AIM:To assess tomographic changes and subclinical edema detection in Fuchs’endothelial corneal dystrophy(FECD)through Scheimpflug tomography in a group of phakic patients contemplating cataract surgery.METHODS:A retr...AIM:To assess tomographic changes and subclinical edema detection in Fuchs’endothelial corneal dystrophy(FECD)through Scheimpflug tomography in a group of phakic patients contemplating cataract surgery.METHODS:A retrospective study was conducted on 30 phakic eyes from patients diagnosed with FECD but without clinical edema,and 59 phakic eyes from a control group without corneal alterations.Comprehensive ophthalmic examinations were conducted,including slitlamp biomicroscopy,corneal specular microscopy(CSM),and Scheimpflug tomography.RESULTS:The study encompassed 30 phakic eyes with FECD(mean age 59.8±13.1y)and 59 control eyes(mean age 61.3±7.7y).The best-corrected visual acuity was higher in the control group compared to the FECD group[0(0,0.08)vs 0.05(0,0.15)logMAR;P=0.042].CSM revealed significant differences between the FECD and control groups in several parameters:number of analyzed cells(26±13 vs 135±42,P<0.001),cell density(2049±376 vs 2479±225 cells/mm2,P<0.001),mean cell area[463(434,544)vs 397(383,431)μm2;P<0.001],coefficient of variation(54.8%±18.7%vs 41.0%±7.2%,P<0.001),and hexagonal cells[0(0,47%)vs 47%(40%,53%),P<0.001].Although often used as a clinical parameter for detecting edema,central corneal thickness measured by CSM showed no significant difference between the FECD and control groups(530±57 vs 546±30μm,P=0.179).Significant differences were noted in various Pentacam measurements between the groups.Specifically,parameters like loss of parallel isopachs(13 vs 0 eyes,P<0.001),displacement of the thinnest point(11 vs 0 eyes,P<0.001),posterior focal depression(25 vs 7 eyes,P<0.001),and increased light scatter[21.4(17.6;23.9)vs 18.0(16.8,21.8),P=0.01]were significantly more prevalent in FECD eyes,reflecting the presence of subclinical edema and loss of corneal transparency.CONCLUSION:Scheimpflug tomography allows for an objective assessment of FECD,offering the capability to detect subclinical edema at an early stage,monitor disease progression,and serve as a predictor of corneal decompensation following cataract surgery.展开更多
BACKGROUND Duchenne muscular dystrophy(DMD)is a neuromuscular disorder caused by mutations in the dystrophin gene.DMD is reported to coexist with other comorbidities,although the occurrence of the triad,autism spectru...BACKGROUND Duchenne muscular dystrophy(DMD)is a neuromuscular disorder caused by mutations in the dystrophin gene.DMD is reported to coexist with other comorbidities,although the occurrence of the triad,autism spectrum disorder(ASD),and epilepsy is very rare.Indeed,only one case of the triad has currently been reported.Here,we present a detailed case report of a ten-year-old boy with DMD,ASD,and epilepsy.We also investigated the dysregulation of miRNAs in this unusual triad(represented as DMD++)compared with a healthy individual and a DMD patient(represented as DMD+)without autism.AIM To understand the differential expression of miRNAs in rare comorbid DMD cases.METHODS The Sequin Form Board test,Gesell's drawing test,multiplex ligation probe amplification,and Vineland Social Maturity Scale were applied to confirm the DMD and ASD.Total RNA was isolated from samples using TRIzol.cDNA was synthesized using the Mir-X^(TM)miRNA First-Strand Synthesis kit.qRT-PCR was performed using SYBR Advantage qPCR Premix.The results were statistically analyzed using one-way analysis of variance with Tukey's ttest.RESULTS miR-146a-5p and miR-132-5p showed significant downregulation in both patient samples.miR-199a-5p and miR-146a-3p showed no change in expression between the diseased and controls.miR-132-3p showed downregulation only in the DMD+sample(0.21±0.04).The decrease in miR-132-3p can result in failed silencing of the phosphatase and tensin homolog-mediated apoptotic pathway,leading to severe skeletal muscle atrophy.Here,the downregulation of miR-132-3p in DMD+is consistent with severe muscle loss and higher disease progression than that in DMD++.DMD++has slower disease progression,and the expression of miRNA involved in inflammatory and apoptotic responses is more similar to that of the control.CONCLUSION Our study shows marked difference in miRNA expression in this rare case of DMD with autism and epilepsy.These miRNAs also serve as regulators of several muscle regeneration,apoptosis,and inflammatory pathways.This study shows the significance of studying miRNAs in such rare cases in a larger cohort to progress in several intervention treatments utilizing miRNAs.展开更多
Objectives:As the Duchenne Muscular Dystrophy(DMD)is a progressive neuromuscular disorder frequently associated with cardiac dysfunction,this study aimed to evaluate the influence of beta-blocker therapy on cardiac au...Objectives:As the Duchenne Muscular Dystrophy(DMD)is a progressive neuromuscular disorder frequently associated with cardiac dysfunction,this study aimed to evaluate the influence of beta-blocker therapy on cardiac autonomic modulation in adolescents withDMDby analyzing heart rate variability(HRV)indices in patients with and without betablockers.Methods:A cross-sectional study was conducted with 90 participants divided into three groups:(1)participants with DMD receiving beta-blocker therapy(DMDB,n=30),(2)participants with DMD without beta-blocker therapy(GMDM,n=30),and(3)age-and sex-matched typically developing participants(GDT,n=30).HRV was assessed using validated beat-to-beat heart rate monitoring(RS800CX,Polar)under controlled conditions.Linear and non-linear HRV indices(including Detrended Fluctuation Analysis and Symbolic Dynamics)were analysed using Kubios HRV software.Results:DMD patients exhibited autonomic impairment,characterized by decreased HRV,increased sympathetic dominance,and reduced parasympathetic modulation.Betablocker therapy was associated with significantly higher Mean Beat-to-beat interval(RR)and lower Mean Heart Rate(HR)compared to the non-beta-blocker DMD group,with values approaching those observed in typically developing participants.Non-linear indices suggested thatDMDpatients receiving beta-blockers demonstrated increased HRV complexity and fractal properties compared to those not receiving beta-blockers,although differences remained between the DMD and control groups.Conclusions:Autonomic dysfunction in DMD is characterized by reduced HRV and altered sympathovagal balance.In our results,beta-blocker therapy was associated with improved HRV and enhanced autonomic control.These findings highlight the potential cardioprotective role of betablockers in DMD management and emphasize the need for further research into optimizing autonomic function in DMD.展开更多
AIM:To analyze the pathogenicity and clinical features of patients in a consanguineous cone-rod dystrophy(CRD)family due to heterozygous variants in the GUCY2D gene.METHODS:Whole exome sequencing was used to screen fo...AIM:To analyze the pathogenicity and clinical features of patients in a consanguineous cone-rod dystrophy(CRD)family due to heterozygous variants in the GUCY2D gene.METHODS:Whole exome sequencing was used to screen for pathogenic genes and candidate pathogenic variants were obtained by bioinformatics analysis.Sanger sequencing was used for validation and familial cosegregation analysis to determine pathogenic variants.Pymol software was applied to produce a 3D structure image of the protein to analyze the structural and functional alterations of the protein.The pathogenicity of genetic variants was evaluated according to ACMG guidelines.RESULTS:The chief clinical symptoms of this proband included obvious visual impairment,protanopia and deuteranopia,peripheral punctate pigment,arteriolar attenuation,structural and functional abnormalities revealed by optical coherence tomography(OCT)and electroretinography(ERG)including thinning of the outer retinal layer,a discontinuous external limiting membrane(ELM)and ellipsoid zone(EZ),granular hyperreflective projections between the retinal pigment epithelium and the interdigitation zone,severe attenuation of photopic responses with mild reduced scotopic responses.Wholeexome sequencing revealed that the proband carried a heterozygous variant of the GUCY2D gene:c.2512C>T:p.Arg838Cys.Three-dimensional molecular structure analysis of the protein revealed that amino acid 838 was mutated from polar positively charged arginine to polar uncharged cysteine,and the spatial structure of the protein changed greatly.Sanger sequencing co-segregation analysis confirmed that such a variant was detected in neither the phenotypically normal parents nor the daughter of the proband,which was presumed to be a de novo one.The variant was determined to be pathogenic according to ACMG guidelines.The heterozygous variant at the same site was detected in the abnormal proband’s son with moderate attenuation of photopic electroretinographic responses and normal scotopic electroretinographic responses,supporting autosomal dominant inheritance.CONCLUSION:The de novo variant causing atypical autosomal dominant CRD is identified in a Chinese consanguineous family and this variant passes through this family in an autosomal dominant mode of inheritance,revealing the complex diversity and unpredictability of the inheritance mode for common single-gene genetic disease.展开更多
BACKGROUND Duchenne muscular dystrophy(DMD)is a severe lethal X-linked monogenic recessive congenital muscular dystrophy caused by various types of mutations in the dystrophin gene(DG).It is one of the most common hum...BACKGROUND Duchenne muscular dystrophy(DMD)is a severe lethal X-linked monogenic recessive congenital muscular dystrophy caused by various types of mutations in the dystrophin gene(DG).It is one of the most common human genetic diseases and the most common type of muscular dystrophy,in part because DG is one of the largest protein-coding genes in the human genome with a relatively high risk of being affected by a large palette of mutations.Long-term corticosteroid therapy(LTCT)with deflazacort started at age 4 is the most accessible and used pharmacological therapy for DMD in Romania."Asea®redox supplement"(ARS)is an approved dietary supplement in the European Union.Several studies have shown that it is a very potent selective NRF2 activator,and thus a very potent,albeit indirect,antioxidant,with no toxicity up to high doses,in contrast to LTCT.CASE SUMMARY This paper presents a 3-case series on the effects of ARS in a 4-year-old,5-year-old and 3-year-old boy all with DMD from Bucharest or Slobozia(Romania).This is the first report of this type worldwide.The parents of these boys had refused LTCT.They were treated with relatively high doses of ARS(3-7 mL/kg/day).For two patients,ARS was administered in combination with medium doses of Lcarnitine and omega-3 fatty acids for various intellectual disabilities.Periodic consults and assessments for rhabdomyolysis,medullar and liver toxicity markers(blood count,gamma-glutamyl transferase,aspartate aminotransferase,alanine transaminase,lactate dehydrogenase,creatine kinase,creatine kinase-MB and serum myoglobin)were performed.In vitro studies showed that ARS is a very potent and selective NRF2 activator,and thus a very potent indirect antioxidant.The in vivo studies also support this main pharmacological mechanism of ARS,with no toxicity at high doses,in contrast with much more toxic corticosteroids which are often refused by parents for their children with DMD.Although they were three distinct ages and carried three distinct DG mutations,from the first months of ARS-based treatment,the children responded similarly to ARS.The rhabdomyolysis markers,which were initially very high,significantly dropped,and there was no evidence for medullar and/or hepatic toxicity in any of the 3 patients.CONCLUSIONS ARS has significant indirect antioxidant effects via NRF2 and deserves extensive trials in children with DMD,as an adjuvant to corticoids or as a substitute in DMD patients who refuse corticoids.Future trials should also focus on ARS as an adjuvant in many types of acute/chronic infectious/non-infectious diseases where cellular oxidative stress is involved.展开更多
Introduction Fuchs endothelial corneal dystrophy(FECD)is an inherited,degenerative disease of the corneal endothelial cells(CECs).It is characterized by a progressive deterioration of endothelial cells,altered extrace...Introduction Fuchs endothelial corneal dystrophy(FECD)is an inherited,degenerative disease of the corneal endothelial cells(CECs).It is characterized by a progressive deterioration of endothelial cells,altered extracellular matrix(ECM)production,and development of guttae(1,2).The presence of guttae has been shown to significantly impair corneal endothelial function,leading to corneal oedema and visual impairment.展开更多
Duchenne muscular dystrophy (DMD) is a hereditary, progressive muscular disorder inherited in an X-linked recessive pattern (Xp21). It typically manifests in childhood and follows a severe, rapid progression. Only mal...Duchenne muscular dystrophy (DMD) is a hereditary, progressive muscular disorder inherited in an X-linked recessive pattern (Xp21). It typically manifests in childhood and follows a severe, rapid progression. Only males are affected, while females are usually carriers. Given the genetic nature of DMD, genetic counseling is an essential service for individuals affected by or at risk of carrying the disease. This service provides not only crucial medical information but also psychosocial support and ongoing management for both patients and their families. Since the discovery of the dystrophin gene in 1987, advancements in molecular genetics have made it possible to precisely identify the genes responsible for many neuromuscular diseases. These developments have revolutionized diagnosis, prognosis, and most importantly, genetic counseling, offering significant benefits for both patients and their families. To highlight the significance of these advancements, this case report focuses on a 10-year-old boy (Y) diagnosed with DMD. It emphasizes the familial nature of the disease, with Y’s two brothers, three cousins, and two maternal uncles also affected, underscoring the inherited pattern of DMD. This reinforces the critical need for early intervention, particularly in regions with high consanguinity, such as North Africa and the Middle East, where genetic counseling and prenatal diagnosis are even more essential. Additionally, the report explores the clinical presentation, diagnostic findings, and promising emerging treatments, including RNA-based therapies, which may play a key role in the future management of DMD. In light of the above, this study underscores the importance of prenatal diagnosis and genetic counseling, particularly in regions like Morocco, where consanguinity rates are notably high. By focusing on preconception care and early genetic intervention, families can be better informed, leading to more effective disease management and support.展开更多
Background: This case report presents a case of bilateral Thiel-Behnke corneal dystrophy in Denmark. Thiel-Behnke is an autosomal dominant inherited epithelial-stromal TGFBI dystrophy causing visual impairment. Method...Background: This case report presents a case of bilateral Thiel-Behnke corneal dystrophy in Denmark. Thiel-Behnke is an autosomal dominant inherited epithelial-stromal TGFBI dystrophy causing visual impairment. Methods and Results: This case study presents a 24-year-old Lithuanian man, with no previous ocular history, who had experienced slowly progressive visual impairment since his childhood. He was examined at the Department of Ophthalmology at Vejle Hospital and Aarhus University Hospital, where he was diagnosed with bilateral Thiel-Behnke corneal dystrophy. Histology confirmed the diagnosis. A lamellar corneal transplantation was performed in the right eye;however, due to epithelial growth under the corneal graft, it was later decided to redo the operation. Following the operations, the patient experienced a visual improvement in best corrected visual acuity (BCVA) from 0.1 (20/25 Snellen equivalent) to 0.3 (20/40 Snellen equivalent) in his right eye. Conclusions: This case of Thiel-Behnke corneal dystrophy is to our knowledge the first reported case in Denmark.展开更多
Duchenne muscular dystrophy(DMD)is a severe neuromuscular disorder caused by mutations in the dystrophin gene,which encodes the essential protein dystrophin.This genetic condition,affecting approximately 1 in 5000 mal...Duchenne muscular dystrophy(DMD)is a severe neuromuscular disorder caused by mutations in the dystrophin gene,which encodes the essential protein dystrophin.This genetic condition,affecting approximately 1 in 5000 male births worldwide(Birnkrant et al.,2018),is characterized by progressive muscle weakness and wasting,leading to premature death in the second or third decade of life(Farini et al.,2016).The absence of dystrophin protein causes instability in the sarcolemma,which predisposes individuals to myonecrosis and activation of inflammatory signaling cascades.Unfortunately,there is currently no effective cure for DMD,and glucocorticoid steroids are commonly used in clinical settings to delay symptom development(Merlini et al.,2003).展开更多
OBJECTIVE： To identify global research trends in stem cell transplantation for treating Duchenne muscular dystrophy using a bibliometric analysis of Web of Science. DATA RETRIEVAL： We performed a bibliometric analys...OBJECTIVE： To identify global research trends in stem cell transplantation for treating Duchenne muscular dystrophy using a bibliometric analysis of Web of Science. DATA RETRIEVAL： We performed a bibliometric analysis of studies on stem cell transplantation for treating Duchenne muscular dystrophy from 2002 to 2011 retrieved from Web of Science. SELECTION CRITERIA： Inclusion criteria： （a） peer-reviewed published articles on stem cell transplantation for treating Duchenne muscular dystrophy indexed in Web of Science; （b） original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material, and news items; and （c） publication between 2002 and 2011. Exclusion criteria： （a） articles that required manual searching or telephone access; （b） documents that were not published in the public domain; and （c） corrected papers. MAIN OUTCOME MEASURES： （1）Annual publication output; （2） distribution according to subject areas; （3） distribution according to journals; （4） distribution according to country; （5） distribution according to institution; （6） distribution according to institution in China; （7） distribution according to institution that cooperated with Chinese institutions; （8） top-cited articles from 2002 to 2006; （9） top-cited articles from 2007 to 2011. RESULTS： A total of 318 publications on stem cell transplantation for treating Duchenne muscular dystrophy were retrieved from Web of Science from 2002 to 2011, of which almost half derived from American authors and institutes. The number of publications has gradually increased over the past 10 years. Most papers appeared in journals with a focus on gene and molecular research, such as Molecular Therapy, Neuromuscular Disorders, and PLoS One. The 10 most-cited papers from 2002 to 2006 were mostly about different kinds of stem cell transplantation for muscle regeneration, while the 10 most-cited papers from 2007 to 2011 were mostly about new techniques of stem cell transplantation for treating Duchenne muscular dystrophy. CONCLUSION： The publications on stem cell transplantation for treating Duchenne muscular dystrophy were relatively few. It also needs more research to confirm that stem cell therapy is a reliable treatment for Duchenne muscular dystrophy.展开更多
AIM: To describe long term follow-up in a family with GUCY2D dominant cone dystrophy. METHODS: Optical coherence tomography scans and fundus autofluorescence images were obtained. Flash and pattern electroretinograms(...AIM: To describe long term follow-up in a family with GUCY2D dominant cone dystrophy. METHODS: Optical coherence tomography scans and fundus autofluorescence images were obtained. Flash and pattern electroretinograms(ERGs) and occipital pattern reversal visual evoked potentials were recorded. RESULTS: Two members of the same family(father and son) were identified to have the heterozygous R838 C mutation in the GUCY2D gene. The father presented at the age of 45 with bilateral bull’s eye maculopathy and temporal disc pallor. Over 13 y of serial follow up visits, the bull’s eye maculopathy progressed gradually into macular atrophy. Electrophysiological tests were significantly degraded suggesting poor macular function. Spectraldomain optical coherence tomography(SD-OCT) scans showed progressive loss and disruption of the ellipsoid layer at the foveal level. His son presented at the age of 16 with bilateral granular retinal pigment epithelial changes in both maculae. Electrophysiological testing was initially borderline normal but has gradually deteriorated to show reduced cone ERGs and macula function. SD-OCT demonstrated gradual macular thinning and atrophy bilaterally. Unlike his father, there was no disruption of the ellipsoid layer.CONCLUSION: Both family members exhibited gradual changes in their fundi, electrophysiological testing and multimodal imaging. Changes were milder than those observed in other mutations of the same gene.展开更多
AIM: To analyze the CYP4V2 mutations in five unrelated Chinese patients with Bietti crystalline corneoretinal dystrophy（BCD） and to provide clinical features of these patients. BCD is a rare monogenic autosomal rece...AIM: To analyze the CYP4V2 mutations in five unrelated Chinese patients with Bietti crystalline corneoretinal dystrophy（BCD） and to provide clinical features of these patients. BCD is a rare monogenic autosomal recessively inherited disorder characterized by the presence of crystals in the retina and retinal pigment epithelium atrophy. Mutations in the CYP4V2 gene have been found to be causative for BCD.METHODS: Ophthalmic examinations were carried out in the affected individuals. Peripheral blood samples were collected and genomic DNA was extracted. All exons and flanking intronic regions of the CYP4V2 gene were amplified with polymerase chain reaction and screened for mutations by direct DNA sequencing. One hundred control chromosomes were also screened to exclude nonpathogenic polymorphisms.RESULTS: Fundus examination revealed the presence of tiny yellowish-sparkling crystals at the posterior pole of the fundus and atrophy of the retinal pigment epithelium in all patients. Choroid neovascularization was noted in one patient. Five different CYP4V2 mutations were identified, including two missense mutations（p.F73 L,p.R400H）, two splice site mutations（c.802-8810del17ins GC, c.1091-2A 】G）, and one single base-pair deletion（p.T479 Tfs X7 or c.1437 del C）. The two splice site mutations were identified in three of the patients with BCD. Mutation p.T479 Tfs X7 was a novel mutation not observed in any of 100 ethnically matched control chromosomes.CONCLUSION: Mutation c.802-8810del17ins GC and c.1091-2A】G are common mutations in Chinese patientswith BCD. Our results expand the allelic heterogeneity of BCD.展开更多
AIMTo identify the disease-causing gene mutation in a Chinese pedigree with autosomal dominant cone-rod dystrophy (adCORD).METHODSA southern Chinese adCORD pedigree including 9 affected individuals was studied. Whole-...AIMTo identify the disease-causing gene mutation in a Chinese pedigree with autosomal dominant cone-rod dystrophy (adCORD).METHODSA southern Chinese adCORD pedigree including 9 affected individuals was studied. Whole-exome sequencing (WES), coupling the Agilent whole-exome capture system to the Illumina HiSeq 2000 DNA sequencing platform was used to search the specific gene mutation in 3 affected family members and 1 unaffected member. After a suggested variant was found through the data analysis, the putative mutation was validated by Sanger DNA sequencing of samples from all available family members.RESULTSThe results of both WES and Sanger sequencing revealed a novel nonsense mutation c.C766T (p.Q256X) within exon 5 of CRX gene which was pathogenic for adCORD in this family. The mutation could affect photoreceptor-specific gene expression with a dominant-negative effect and resulted in loss of the OTX tail, thus the mutant protein occupies the CRX-binding site in target promoters without establishing an interaction and, consequently, may block transactivation.CONCLUSIONAll modes of Mendelian inheritance in CORD have been observed, and genetic heterogeneity is a hallmark of CORD. Therefore, conventional genetic diagnosis of CORD would be time-consuming and labor-intensive. Our study indicated the robustness and cost-effectiveness of WES in the genetic diagnosis of CORD.展开更多
AIM:To reveal the importance of TGFBI gene screening for candidates with a family history of corneal disease or granular opacities in corneal stroma before refractive surgery.METHODS:A 37-year-old male(proband)underwe...AIM:To reveal the importance of TGFBI gene screening for candidates with a family history of corneal disease or granular opacities in corneal stroma before refractive surgery.METHODS:A 37-year-old male(proband)underwent bilateral laser-assisted in situ keratomileusis(LASIK)in 2002,with right vision decreased significantly in 2006.The proband and other 32 members of the family underwent a detailed ophthalmic examination,including vision acuity,intraocular pressure,slit-lamp photograph,fundus examination,optical coherence tomography(OCT)of cornea,and in vivo confocal microscope(IVCM)and peripheral blood was used for genomic DNA extraction.Seventeen TGFBI gene exons were analyzed via polymerase chain reaction amplification and direct sequencing.RESULTS:Slit-lamp,IVCM,and OCT images showed that a large amount of dense and confluent granular opaque were seen at the interfaces of the flap and remnant stromal bed in right and light degree in left eye.Sanger sequencing showed that there was a 371 G>A mutation(CGC>CAC)in exon 4,which indicated that he harbored a heterozygote R124 H mutation,identifying the diagnosis of Avellino corneal dystrophy(ACD).Among the other 32 family members,6 of them harbored the identical mutation to that in the proband.CONCLUSION:ACD will worsen and recur after LASIK.Preoperative gene-screening for TGFBI mutations is important in diagnosing ACD.展开更多
Background:To determine the effectiveness of resistive range of motion exercises in improving muscle strength and functional abilities in Duchenne muscular dystrophy.The study was also aimed to determine if resistive ...Background:To determine the effectiveness of resistive range of motion exercises in improving muscle strength and functional abilities in Duchenne muscular dystrophy.The study was also aimed to determine if resistive range of motion exercises can slow down the progression of the disease.Methods:A seven-year-old male child was diagnosed with Duchenne muscle dystrophy presented to outpatient physiotherapy clinic.The patient was presented with difficulty in stair climbing,sitting up from the floor,fatigue,and muscle weakness specifically weakness in the proximal limb muscles.The progressive resistive range of motion training was implemented for four years to improve muscle strength and functional abilities.The medical research council grading scale,north ambulatory assessment scale,and creatine kinase were used to evaluate muscle strength,functional abilities,and creatine kinase levels.Results:The muscular strength and functional abilities did not improve after four years of exercise training.The creatine kinase levels were decreased over the period of four years.Conclusion:Resistive range of motion exercises are helpful in maintaining the muscular strength and functional abilities in Duchenne muscular dystrophy.展开更多
Quantitative magnetic resonance image(MRI)in individual muscles may be useful for monitoring disease progression in Duchenne muscular dystrophy(DMD).The purpose of this study w批to measure丁2 relaxation time of thigh ...Quantitative magnetic resonance image(MRI)in individual muscles may be useful for monitoring disease progression in Duchenne muscular dystrophy(DMD).The purpose of this study w批to measure丁2 relaxation time of thigh muscles in children with DMD and healthy boys,and to correlate the T2 relaxation time of muscles with the fat fraction(FF)at quantitative magnetic resonance and results of clinical assessment.Thirty-two boys with DMD and 18 healthy boys were evaluated with T2 mapping and three-point Dixon MRI.Age,body mass index(BMI),muscle strength assessment,timed functional tests(time to walk or run 10 metres,rise from the floor and ascend four stairs),and the North Star Ambulatory Assessment(NSAA)were evaluated.Spearman’s correlation was used to assess the relationships between FF and clinical assessments and T2 relaxation time.The mean T2 relaxation time of thigh muscles in DMD was significantly longer than that in the control group(P<0.05),except for the gracilis(P=0.952).The gracilis,sartorius and adductor longus were relatively spared by fatty infiltration in DMD patients.The T2 relaxation time was correlated significantly with the mean FF in all muscles.Age,BMI,total muscle strength score,timed functional tests and NSAA were significantly correlated with the overall mean T2 relaxation time.T2 mapping may prove clinically useful in monitoring muscle changes as a result of the disease process and in predicting the outcome of DMD patients.展开更多
Adipose-derived stem cells have been shown to promote peripheral nerve regeneration through the paracrine secretion of neurotrophic factors. However, it is unclear whether these cells can promote myogenic differentiat...Adipose-derived stem cells have been shown to promote peripheral nerve regeneration through the paracrine secretion of neurotrophic factors. However, it is unclear whether these cells can promote myogenic differentiation in muscular dystrophy. Adipose-derived stem cells （6 × 106） were injected into the gastrocnemius muscle of mdx mice at various sites. Dystrophin expression was found in the muscle fibers. Phosphorylation levels of Akt, mammalian target of rapamycin （mTOR）, eIF-4E binding protein 1 and $6 kinase 1 were increased, and the Akt/mTOR pathway was activated. Simultaneously, myogenin levels were increased, whereas cleaved caspase 3 and vimentin levels were decreased. Necrosis and fibrosis were reduced in the muscle fibers. These findings suggest that adipose-derived stem cells promote the re- generation and survival of muscle cells by inhibiting apoptosis and fibrosis, thereby alleviating muscle damage in muscular dystrophy.展开更多
Due to their relative abundance,stable biological properties and excellent reproductive activity,umbilical cord mesenchymal stem cells have previously been utilized for the treatment of Duchenne muscular dystrophy,whi...Due to their relative abundance,stable biological properties and excellent reproductive activity,umbilical cord mesenchymal stem cells have previously been utilized for the treatment of Duchenne muscular dystrophy,which is a muscular atrophy disease.Three patients who were clinically and pathologically diagnosed with Duchenne muscular dystrophy were transplanted with umbilical cord mesenchymal stem cells by intravenous infusion,in combination with multi-point intramuscular injection.They were followed up for 12 months after cell transplantation.Results showed that clinical symptoms significantly improved,daily living activity and muscle strength were enhanced,the sero-enzyme,electromyogram,and MRI scans showed improvement,and dystrophin was expressed in the muscle cell membrane.Hematoxylin-eosin staining of a muscle biopsy revealed that muscle fibers were well arranged,fibrous degeneration was alleviated,and fat infiltration was improved.These pieces of evidence suggest that umbilical cord mesenchymal stem cell transplantation can be considered as a new regimen for Duchenne muscular dystrophy.展开更多
AIM： To uncover the mutations profile of transforming growth factor beta-induced （TGFBI） gene in Chinese corneal dystrophy patients and further investigate the characteristics of genotype-phenotype correlations. M...AIM： To uncover the mutations profile of transforming growth factor beta-induced （TGFBI） gene in Chinese corneal dystrophy patients and further investigate the characteristics of genotype-phenotype correlations. METHODS： Forty-two subjects （6 unrelated families including 15 patients and 8 unaffected members, and 19 sporadic patients） of Chinese origin were subjected to phenotypic and genotypic characterization. The corneal phenotypes of patients were documented by slit lamp photography. Mutation screening of the coding regions of TGFBI was performed by direct sequencing. RESULTS： We detected four corneal dystrophy types. The most frequent phenotypes were granular corneal dystrophy （GCD） （including 3 families and 8 sporadic patients） and lattice corneal dystrophy （LCD） （including 2 families and 9 sporadic patients）. The next phenotypes were corneal dystrophy of Bowman layer （CDB） （1 family and 1 sporadic patient） and epithelial basement membrane dystrophy （EBMD） （1 sporadic patient）. Six distinct mutations responsible for TGFBI corneal dystrophies were identified in 30 individuals with corneal dystrophies. Those were, p.R124H mutation in 1 family and 2 sporadic patients with GCD, p.R555W mutation in 2 families and 3 sporadic patients with GCD, p.R124C mutation in 2 families and 7 sporadic patients with LCD, p.A620D mutation in 1 sporadic patient with LCD, p.H626R mutation in 1 sporadic patient with LCD, and p.R555Q in 1 family and 1 sporadic patient with CDB. No mutation was detected in the remaining 3 atypical GCD patients and 1 EBMD patient, CONCLUSION： GCD and LCD are the most frequent phenotypes in Chinese population. R555W was the most common mutation for GCD; R124C was the most common mutation for LCD, Our findings extend the mutational spectrum of TFGBI , and this is the extensively delineated TGFBI mutation profile associated with the various corneal dystrophies in the Chinese population.展开更多
文摘AIM:To assess tomographic changes and subclinical edema detection in Fuchs’endothelial corneal dystrophy(FECD)through Scheimpflug tomography in a group of phakic patients contemplating cataract surgery.METHODS:A retrospective study was conducted on 30 phakic eyes from patients diagnosed with FECD but without clinical edema,and 59 phakic eyes from a control group without corneal alterations.Comprehensive ophthalmic examinations were conducted,including slitlamp biomicroscopy,corneal specular microscopy(CSM),and Scheimpflug tomography.RESULTS:The study encompassed 30 phakic eyes with FECD(mean age 59.8±13.1y)and 59 control eyes(mean age 61.3±7.7y).The best-corrected visual acuity was higher in the control group compared to the FECD group[0(0,0.08)vs 0.05(0,0.15)logMAR;P=0.042].CSM revealed significant differences between the FECD and control groups in several parameters:number of analyzed cells(26±13 vs 135±42,P<0.001),cell density(2049±376 vs 2479±225 cells/mm2,P<0.001),mean cell area[463(434,544)vs 397(383,431)μm2;P<0.001],coefficient of variation(54.8%±18.7%vs 41.0%±7.2%,P<0.001),and hexagonal cells[0(0,47%)vs 47%(40%,53%),P<0.001].Although often used as a clinical parameter for detecting edema,central corneal thickness measured by CSM showed no significant difference between the FECD and control groups(530±57 vs 546±30μm,P=0.179).Significant differences were noted in various Pentacam measurements between the groups.Specifically,parameters like loss of parallel isopachs(13 vs 0 eyes,P<0.001),displacement of the thinnest point(11 vs 0 eyes,P<0.001),posterior focal depression(25 vs 7 eyes,P<0.001),and increased light scatter[21.4(17.6;23.9)vs 18.0(16.8,21.8),P=0.01]were significantly more prevalent in FECD eyes,reflecting the presence of subclinical edema and loss of corneal transparency.CONCLUSION:Scheimpflug tomography allows for an objective assessment of FECD,offering the capability to detect subclinical edema at an early stage,monitor disease progression,and serve as a predictor of corneal decompensation following cataract surgery.
文摘BACKGROUND Duchenne muscular dystrophy(DMD)is a neuromuscular disorder caused by mutations in the dystrophin gene.DMD is reported to coexist with other comorbidities,although the occurrence of the triad,autism spectrum disorder(ASD),and epilepsy is very rare.Indeed,only one case of the triad has currently been reported.Here,we present a detailed case report of a ten-year-old boy with DMD,ASD,and epilepsy.We also investigated the dysregulation of miRNAs in this unusual triad(represented as DMD++)compared with a healthy individual and a DMD patient(represented as DMD+)without autism.AIM To understand the differential expression of miRNAs in rare comorbid DMD cases.METHODS The Sequin Form Board test,Gesell's drawing test,multiplex ligation probe amplification,and Vineland Social Maturity Scale were applied to confirm the DMD and ASD.Total RNA was isolated from samples using TRIzol.cDNA was synthesized using the Mir-X^(TM)miRNA First-Strand Synthesis kit.qRT-PCR was performed using SYBR Advantage qPCR Premix.The results were statistically analyzed using one-way analysis of variance with Tukey's ttest.RESULTS miR-146a-5p and miR-132-5p showed significant downregulation in both patient samples.miR-199a-5p and miR-146a-3p showed no change in expression between the diseased and controls.miR-132-3p showed downregulation only in the DMD+sample(0.21±0.04).The decrease in miR-132-3p can result in failed silencing of the phosphatase and tensin homolog-mediated apoptotic pathway,leading to severe skeletal muscle atrophy.Here,the downregulation of miR-132-3p in DMD+is consistent with severe muscle loss and higher disease progression than that in DMD++.DMD++has slower disease progression,and the expression of miRNA involved in inflammatory and apoptotic responses is more similar to that of the control.CONCLUSION Our study shows marked difference in miRNA expression in this rare case of DMD with autism and epilepsy.These miRNAs also serve as regulators of several muscle regeneration,apoptosis,and inflammatory pathways.This study shows the significance of studying miRNAs in such rare cases in a larger cohort to progress in several intervention treatments utilizing miRNAs.
文摘Objectives:As the Duchenne Muscular Dystrophy(DMD)is a progressive neuromuscular disorder frequently associated with cardiac dysfunction,this study aimed to evaluate the influence of beta-blocker therapy on cardiac autonomic modulation in adolescents withDMDby analyzing heart rate variability(HRV)indices in patients with and without betablockers.Methods:A cross-sectional study was conducted with 90 participants divided into three groups:(1)participants with DMD receiving beta-blocker therapy(DMDB,n=30),(2)participants with DMD without beta-blocker therapy(GMDM,n=30),and(3)age-and sex-matched typically developing participants(GDT,n=30).HRV was assessed using validated beat-to-beat heart rate monitoring(RS800CX,Polar)under controlled conditions.Linear and non-linear HRV indices(including Detrended Fluctuation Analysis and Symbolic Dynamics)were analysed using Kubios HRV software.Results:DMD patients exhibited autonomic impairment,characterized by decreased HRV,increased sympathetic dominance,and reduced parasympathetic modulation.Betablocker therapy was associated with significantly higher Mean Beat-to-beat interval(RR)and lower Mean Heart Rate(HR)compared to the non-beta-blocker DMD group,with values approaching those observed in typically developing participants.Non-linear indices suggested thatDMDpatients receiving beta-blockers demonstrated increased HRV complexity and fractal properties compared to those not receiving beta-blockers,although differences remained between the DMD and control groups.Conclusions:Autonomic dysfunction in DMD is characterized by reduced HRV and altered sympathovagal balance.In our results,beta-blocker therapy was associated with improved HRV and enhanced autonomic control.These findings highlight the potential cardioprotective role of betablockers in DMD management and emphasize the need for further research into optimizing autonomic function in DMD.
基金Supported by the National Natural Science Foundation of China(No.82260206)Natural Science Foundation of Ningxia(No.2022AAC03387)+1 种基金Major Achievement Transformation Project of Ningxia Hui Autonomous Region(No.2022CJE09011)the Key Research Development Project of Ningxia Hui Autonomous Region(No.2024BEG02017).
文摘AIM:To analyze the pathogenicity and clinical features of patients in a consanguineous cone-rod dystrophy(CRD)family due to heterozygous variants in the GUCY2D gene.METHODS:Whole exome sequencing was used to screen for pathogenic genes and candidate pathogenic variants were obtained by bioinformatics analysis.Sanger sequencing was used for validation and familial cosegregation analysis to determine pathogenic variants.Pymol software was applied to produce a 3D structure image of the protein to analyze the structural and functional alterations of the protein.The pathogenicity of genetic variants was evaluated according to ACMG guidelines.RESULTS:The chief clinical symptoms of this proband included obvious visual impairment,protanopia and deuteranopia,peripheral punctate pigment,arteriolar attenuation,structural and functional abnormalities revealed by optical coherence tomography(OCT)and electroretinography(ERG)including thinning of the outer retinal layer,a discontinuous external limiting membrane(ELM)and ellipsoid zone(EZ),granular hyperreflective projections between the retinal pigment epithelium and the interdigitation zone,severe attenuation of photopic responses with mild reduced scotopic responses.Wholeexome sequencing revealed that the proband carried a heterozygous variant of the GUCY2D gene:c.2512C>T:p.Arg838Cys.Three-dimensional molecular structure analysis of the protein revealed that amino acid 838 was mutated from polar positively charged arginine to polar uncharged cysteine,and the spatial structure of the protein changed greatly.Sanger sequencing co-segregation analysis confirmed that such a variant was detected in neither the phenotypically normal parents nor the daughter of the proband,which was presumed to be a de novo one.The variant was determined to be pathogenic according to ACMG guidelines.The heterozygous variant at the same site was detected in the abnormal proband’s son with moderate attenuation of photopic electroretinographic responses and normal scotopic electroretinographic responses,supporting autosomal dominant inheritance.CONCLUSION:The de novo variant causing atypical autosomal dominant CRD is identified in a Chinese consanguineous family and this variant passes through this family in an autosomal dominant mode of inheritance,revealing the complex diversity and unpredictability of the inheritance mode for common single-gene genetic disease.
文摘BACKGROUND Duchenne muscular dystrophy(DMD)is a severe lethal X-linked monogenic recessive congenital muscular dystrophy caused by various types of mutations in the dystrophin gene(DG).It is one of the most common human genetic diseases and the most common type of muscular dystrophy,in part because DG is one of the largest protein-coding genes in the human genome with a relatively high risk of being affected by a large palette of mutations.Long-term corticosteroid therapy(LTCT)with deflazacort started at age 4 is the most accessible and used pharmacological therapy for DMD in Romania."Asea®redox supplement"(ARS)is an approved dietary supplement in the European Union.Several studies have shown that it is a very potent selective NRF2 activator,and thus a very potent,albeit indirect,antioxidant,with no toxicity up to high doses,in contrast to LTCT.CASE SUMMARY This paper presents a 3-case series on the effects of ARS in a 4-year-old,5-year-old and 3-year-old boy all with DMD from Bucharest or Slobozia(Romania).This is the first report of this type worldwide.The parents of these boys had refused LTCT.They were treated with relatively high doses of ARS(3-7 mL/kg/day).For two patients,ARS was administered in combination with medium doses of Lcarnitine and omega-3 fatty acids for various intellectual disabilities.Periodic consults and assessments for rhabdomyolysis,medullar and liver toxicity markers(blood count,gamma-glutamyl transferase,aspartate aminotransferase,alanine transaminase,lactate dehydrogenase,creatine kinase,creatine kinase-MB and serum myoglobin)were performed.In vitro studies showed that ARS is a very potent and selective NRF2 activator,and thus a very potent indirect antioxidant.The in vivo studies also support this main pharmacological mechanism of ARS,with no toxicity at high doses,in contrast with much more toxic corticosteroids which are often refused by parents for their children with DMD.Although they were three distinct ages and carried three distinct DG mutations,from the first months of ARS-based treatment,the children responded similarly to ARS.The rhabdomyolysis markers,which were initially very high,significantly dropped,and there was no evidence for medullar and/or hepatic toxicity in any of the 3 patients.CONCLUSIONS ARS has significant indirect antioxidant effects via NRF2 and deserves extensive trials in children with DMD,as an adjuvant to corticoids or as a substitute in DMD patients who refuse corticoids.Future trials should also focus on ARS as an adjuvant in many types of acute/chronic infectious/non-infectious diseases where cellular oxidative stress is involved.
文摘Introduction Fuchs endothelial corneal dystrophy(FECD)is an inherited,degenerative disease of the corneal endothelial cells(CECs).It is characterized by a progressive deterioration of endothelial cells,altered extracellular matrix(ECM)production,and development of guttae(1,2).The presence of guttae has been shown to significantly impair corneal endothelial function,leading to corneal oedema and visual impairment.
文摘Duchenne muscular dystrophy (DMD) is a hereditary, progressive muscular disorder inherited in an X-linked recessive pattern (Xp21). It typically manifests in childhood and follows a severe, rapid progression. Only males are affected, while females are usually carriers. Given the genetic nature of DMD, genetic counseling is an essential service for individuals affected by or at risk of carrying the disease. This service provides not only crucial medical information but also psychosocial support and ongoing management for both patients and their families. Since the discovery of the dystrophin gene in 1987, advancements in molecular genetics have made it possible to precisely identify the genes responsible for many neuromuscular diseases. These developments have revolutionized diagnosis, prognosis, and most importantly, genetic counseling, offering significant benefits for both patients and their families. To highlight the significance of these advancements, this case report focuses on a 10-year-old boy (Y) diagnosed with DMD. It emphasizes the familial nature of the disease, with Y’s two brothers, three cousins, and two maternal uncles also affected, underscoring the inherited pattern of DMD. This reinforces the critical need for early intervention, particularly in regions with high consanguinity, such as North Africa and the Middle East, where genetic counseling and prenatal diagnosis are even more essential. Additionally, the report explores the clinical presentation, diagnostic findings, and promising emerging treatments, including RNA-based therapies, which may play a key role in the future management of DMD. In light of the above, this study underscores the importance of prenatal diagnosis and genetic counseling, particularly in regions like Morocco, where consanguinity rates are notably high. By focusing on preconception care and early genetic intervention, families can be better informed, leading to more effective disease management and support.
文摘Background: This case report presents a case of bilateral Thiel-Behnke corneal dystrophy in Denmark. Thiel-Behnke is an autosomal dominant inherited epithelial-stromal TGFBI dystrophy causing visual impairment. Methods and Results: This case study presents a 24-year-old Lithuanian man, with no previous ocular history, who had experienced slowly progressive visual impairment since his childhood. He was examined at the Department of Ophthalmology at Vejle Hospital and Aarhus University Hospital, where he was diagnosed with bilateral Thiel-Behnke corneal dystrophy. Histology confirmed the diagnosis. A lamellar corneal transplantation was performed in the right eye;however, due to epithelial growth under the corneal graft, it was later decided to redo the operation. Following the operations, the patient experienced a visual improvement in best corrected visual acuity (BCVA) from 0.1 (20/25 Snellen equivalent) to 0.3 (20/40 Snellen equivalent) in his right eye. Conclusions: This case of Thiel-Behnke corneal dystrophy is to our knowledge the first reported case in Denmark.
基金supported by grants from National Natural Science Foundation of China(82202052,82230039,U2005201,81870902,82001217,31925016,and 82021001)Major Scientific Research Project for Middle-age and Youth of Fujian Provincial Health Commission grant(2021ZQNZD003)+2 种基金Major Scientific Research Project of Fujian Provincial Health Commission grant(2022ZD01002)Joint Funds for the Innovation of Science and Technology of Fujian Province(2018Y9082)the Youth Scientific Research。
文摘Duchenne muscular dystrophy(DMD)is a severe neuromuscular disorder caused by mutations in the dystrophin gene,which encodes the essential protein dystrophin.This genetic condition,affecting approximately 1 in 5000 male births worldwide(Birnkrant et al.,2018),is characterized by progressive muscle weakness and wasting,leading to premature death in the second or third decade of life(Farini et al.,2016).The absence of dystrophin protein causes instability in the sarcolemma,which predisposes individuals to myonecrosis and activation of inflammatory signaling cascades.Unfortunately,there is currently no effective cure for DMD,and glucocorticoid steroids are commonly used in clinical settings to delay symptom development(Merlini et al.,2003).
基金supported by the Key TechnologiesR & D Program of Liaoning Province,No.2008225009.
文摘OBJECTIVE： To identify global research trends in stem cell transplantation for treating Duchenne muscular dystrophy using a bibliometric analysis of Web of Science. DATA RETRIEVAL： We performed a bibliometric analysis of studies on stem cell transplantation for treating Duchenne muscular dystrophy from 2002 to 2011 retrieved from Web of Science. SELECTION CRITERIA： Inclusion criteria： （a） peer-reviewed published articles on stem cell transplantation for treating Duchenne muscular dystrophy indexed in Web of Science; （b） original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material, and news items; and （c） publication between 2002 and 2011. Exclusion criteria： （a） articles that required manual searching or telephone access; （b） documents that were not published in the public domain; and （c） corrected papers. MAIN OUTCOME MEASURES： （1）Annual publication output; （2） distribution according to subject areas; （3） distribution according to journals; （4） distribution according to country; （5） distribution according to institution; （6） distribution according to institution in China; （7） distribution according to institution that cooperated with Chinese institutions; （8） top-cited articles from 2002 to 2006; （9） top-cited articles from 2007 to 2011. RESULTS： A total of 318 publications on stem cell transplantation for treating Duchenne muscular dystrophy were retrieved from Web of Science from 2002 to 2011, of which almost half derived from American authors and institutes. The number of publications has gradually increased over the past 10 years. Most papers appeared in journals with a focus on gene and molecular research, such as Molecular Therapy, Neuromuscular Disorders, and PLoS One. The 10 most-cited papers from 2002 to 2006 were mostly about different kinds of stem cell transplantation for muscle regeneration, while the 10 most-cited papers from 2007 to 2011 were mostly about new techniques of stem cell transplantation for treating Duchenne muscular dystrophy. CONCLUSION： The publications on stem cell transplantation for treating Duchenne muscular dystrophy were relatively few. It also needs more research to confirm that stem cell therapy is a reliable treatment for Duchenne muscular dystrophy.
基金Supported by Fight Against Blindness Charity Organization
文摘AIM: To describe long term follow-up in a family with GUCY2D dominant cone dystrophy. METHODS: Optical coherence tomography scans and fundus autofluorescence images were obtained. Flash and pattern electroretinograms(ERGs) and occipital pattern reversal visual evoked potentials were recorded. RESULTS: Two members of the same family(father and son) were identified to have the heterozygous R838 C mutation in the GUCY2D gene. The father presented at the age of 45 with bilateral bull’s eye maculopathy and temporal disc pallor. Over 13 y of serial follow up visits, the bull’s eye maculopathy progressed gradually into macular atrophy. Electrophysiological tests were significantly degraded suggesting poor macular function. Spectraldomain optical coherence tomography(SD-OCT) scans showed progressive loss and disruption of the ellipsoid layer at the foveal level. His son presented at the age of 16 with bilateral granular retinal pigment epithelial changes in both maculae. Electrophysiological testing was initially borderline normal but has gradually deteriorated to show reduced cone ERGs and macula function. SD-OCT demonstrated gradual macular thinning and atrophy bilaterally. Unlike his father, there was no disruption of the ellipsoid layer.CONCLUSION: Both family members exhibited gradual changes in their fundi, electrophysiological testing and multimodal imaging. Changes were milder than those observed in other mutations of the same gene.
文摘AIM: To analyze the CYP4V2 mutations in five unrelated Chinese patients with Bietti crystalline corneoretinal dystrophy（BCD） and to provide clinical features of these patients. BCD is a rare monogenic autosomal recessively inherited disorder characterized by the presence of crystals in the retina and retinal pigment epithelium atrophy. Mutations in the CYP4V2 gene have been found to be causative for BCD.METHODS: Ophthalmic examinations were carried out in the affected individuals. Peripheral blood samples were collected and genomic DNA was extracted. All exons and flanking intronic regions of the CYP4V2 gene were amplified with polymerase chain reaction and screened for mutations by direct DNA sequencing. One hundred control chromosomes were also screened to exclude nonpathogenic polymorphisms.RESULTS: Fundus examination revealed the presence of tiny yellowish-sparkling crystals at the posterior pole of the fundus and atrophy of the retinal pigment epithelium in all patients. Choroid neovascularization was noted in one patient. Five different CYP4V2 mutations were identified, including two missense mutations（p.F73 L,p.R400H）, two splice site mutations（c.802-8810del17ins GC, c.1091-2A 】G）, and one single base-pair deletion（p.T479 Tfs X7 or c.1437 del C）. The two splice site mutations were identified in three of the patients with BCD. Mutation p.T479 Tfs X7 was a novel mutation not observed in any of 100 ethnically matched control chromosomes.CONCLUSION: Mutation c.802-8810del17ins GC and c.1091-2A】G are common mutations in Chinese patientswith BCD. Our results expand the allelic heterogeneity of BCD.
基金Supported by the Zhejiang Provincial Natural Science Foundation of China (No.LY12H12001)the Ningbo Key Foundation of Society Development (No.2014C50091)+2 种基金the Ningbo Natural Science Foundation (No.2012A610192)the Ningbo Yinzhou District S&T Foundation (No.YK2013-90)the Shenzhen Municipal Government of China (No.GJHZ20130417140916986)
文摘AIMTo identify the disease-causing gene mutation in a Chinese pedigree with autosomal dominant cone-rod dystrophy (adCORD).METHODSA southern Chinese adCORD pedigree including 9 affected individuals was studied. Whole-exome sequencing (WES), coupling the Agilent whole-exome capture system to the Illumina HiSeq 2000 DNA sequencing platform was used to search the specific gene mutation in 3 affected family members and 1 unaffected member. After a suggested variant was found through the data analysis, the putative mutation was validated by Sanger DNA sequencing of samples from all available family members.RESULTSThe results of both WES and Sanger sequencing revealed a novel nonsense mutation c.C766T (p.Q256X) within exon 5 of CRX gene which was pathogenic for adCORD in this family. The mutation could affect photoreceptor-specific gene expression with a dominant-negative effect and resulted in loss of the OTX tail, thus the mutant protein occupies the CRX-binding site in target promoters without establishing an interaction and, consequently, may block transactivation.CONCLUSIONAll modes of Mendelian inheritance in CORD have been observed, and genetic heterogeneity is a hallmark of CORD. Therefore, conventional genetic diagnosis of CORD would be time-consuming and labor-intensive. Our study indicated the robustness and cost-effectiveness of WES in the genetic diagnosis of CORD.
基金the National Natural Science Foundation of China(No.U20A20363No.81970776)the Natural Science Foundation of Heilongjiang Province,China(No.LH2020H039)。
文摘AIM:To reveal the importance of TGFBI gene screening for candidates with a family history of corneal disease or granular opacities in corneal stroma before refractive surgery.METHODS:A 37-year-old male(proband)underwent bilateral laser-assisted in situ keratomileusis(LASIK)in 2002,with right vision decreased significantly in 2006.The proband and other 32 members of the family underwent a detailed ophthalmic examination,including vision acuity,intraocular pressure,slit-lamp photograph,fundus examination,optical coherence tomography(OCT)of cornea,and in vivo confocal microscope(IVCM)and peripheral blood was used for genomic DNA extraction.Seventeen TGFBI gene exons were analyzed via polymerase chain reaction amplification and direct sequencing.RESULTS:Slit-lamp,IVCM,and OCT images showed that a large amount of dense and confluent granular opaque were seen at the interfaces of the flap and remnant stromal bed in right and light degree in left eye.Sanger sequencing showed that there was a 371 G>A mutation(CGC>CAC)in exon 4,which indicated that he harbored a heterozygote R124 H mutation,identifying the diagnosis of Avellino corneal dystrophy(ACD).Among the other 32 family members,6 of them harbored the identical mutation to that in the proband.CONCLUSION:ACD will worsen and recur after LASIK.Preoperative gene-screening for TGFBI mutations is important in diagnosing ACD.
文摘Background:To determine the effectiveness of resistive range of motion exercises in improving muscle strength and functional abilities in Duchenne muscular dystrophy.The study was also aimed to determine if resistive range of motion exercises can slow down the progression of the disease.Methods:A seven-year-old male child was diagnosed with Duchenne muscle dystrophy presented to outpatient physiotherapy clinic.The patient was presented with difficulty in stair climbing,sitting up from the floor,fatigue,and muscle weakness specifically weakness in the proximal limb muscles.The progressive resistive range of motion training was implemented for four years to improve muscle strength and functional abilities.The medical research council grading scale,north ambulatory assessment scale,and creatine kinase were used to evaluate muscle strength,functional abilities,and creatine kinase levels.Results:The muscular strength and functional abilities did not improve after four years of exercise training.The creatine kinase levels were decreased over the period of four years.Conclusion:Resistive range of motion exercises are helpful in maintaining the muscular strength and functional abilities in Duchenne muscular dystrophy.
文摘Quantitative magnetic resonance image(MRI)in individual muscles may be useful for monitoring disease progression in Duchenne muscular dystrophy(DMD).The purpose of this study w批to measure丁2 relaxation time of thigh muscles in children with DMD and healthy boys,and to correlate the T2 relaxation time of muscles with the fat fraction(FF)at quantitative magnetic resonance and results of clinical assessment.Thirty-two boys with DMD and 18 healthy boys were evaluated with T2 mapping and three-point Dixon MRI.Age,body mass index(BMI),muscle strength assessment,timed functional tests(time to walk or run 10 metres,rise from the floor and ascend four stairs),and the North Star Ambulatory Assessment(NSAA)were evaluated.Spearman’s correlation was used to assess the relationships between FF and clinical assessments and T2 relaxation time.The mean T2 relaxation time of thigh muscles in DMD was significantly longer than that in the control group(P<0.05),except for the gracilis(P=0.952).The gracilis,sartorius and adductor longus were relatively spared by fatty infiltration in DMD patients.The T2 relaxation time was correlated significantly with the mean FF in all muscles.Age,BMI,total muscle strength score,timed functional tests and NSAA were significantly correlated with the overall mean T2 relaxation time.T2 mapping may prove clinically useful in monitoring muscle changes as a result of the disease process and in predicting the outcome of DMD patients.
基金supported by the National Natural Science Foundation of China,No.30370510,30870851,81271401the Joint Fund of National Natural Science Foundation of ChinaNatural Science Foundation of Guangdong Province of China,No.U1032004
文摘Adipose-derived stem cells have been shown to promote peripheral nerve regeneration through the paracrine secretion of neurotrophic factors. However, it is unclear whether these cells can promote myogenic differentiation in muscular dystrophy. Adipose-derived stem cells （6 × 106） were injected into the gastrocnemius muscle of mdx mice at various sites. Dystrophin expression was found in the muscle fibers. Phosphorylation levels of Akt, mammalian target of rapamycin （mTOR）, eIF-4E binding protein 1 and $6 kinase 1 were increased, and the Akt/mTOR pathway was activated. Simultaneously, myogenin levels were increased, whereas cleaved caspase 3 and vimentin levels were decreased. Necrosis and fibrosis were reduced in the muscle fibers. These findings suggest that adipose-derived stem cells promote the re- generation and survival of muscle cells by inhibiting apoptosis and fibrosis, thereby alleviating muscle damage in muscular dystrophy.
基金a grant by Key Projects of Liaoning Province, No. 2008225009
文摘Due to their relative abundance,stable biological properties and excellent reproductive activity,umbilical cord mesenchymal stem cells have previously been utilized for the treatment of Duchenne muscular dystrophy,which is a muscular atrophy disease.Three patients who were clinically and pathologically diagnosed with Duchenne muscular dystrophy were transplanted with umbilical cord mesenchymal stem cells by intravenous infusion,in combination with multi-point intramuscular injection.They were followed up for 12 months after cell transplantation.Results showed that clinical symptoms significantly improved,daily living activity and muscle strength were enhanced,the sero-enzyme,electromyogram,and MRI scans showed improvement,and dystrophin was expressed in the muscle cell membrane.Hematoxylin-eosin staining of a muscle biopsy revealed that muscle fibers were well arranged,fibrous degeneration was alleviated,and fat infiltration was improved.These pieces of evidence suggest that umbilical cord mesenchymal stem cell transplantation can be considered as a new regimen for Duchenne muscular dystrophy.
基金Supported by the National Natural Science Foundation of China (No.81370990)the Young and MiddleAged Scientists Research Awards Fund of Shandong Province, China (No. BS2013YY013, No. BS2015YY014)the Science and Technology Foundation of Shinan District, Qingdao, Shandong Province, China (No. 2013-13-014-YY)
文摘AIM： To uncover the mutations profile of transforming growth factor beta-induced （TGFBI） gene in Chinese corneal dystrophy patients and further investigate the characteristics of genotype-phenotype correlations. METHODS： Forty-two subjects （6 unrelated families including 15 patients and 8 unaffected members, and 19 sporadic patients） of Chinese origin were subjected to phenotypic and genotypic characterization. The corneal phenotypes of patients were documented by slit lamp photography. Mutation screening of the coding regions of TGFBI was performed by direct sequencing. RESULTS： We detected four corneal dystrophy types. The most frequent phenotypes were granular corneal dystrophy （GCD） （including 3 families and 8 sporadic patients） and lattice corneal dystrophy （LCD） （including 2 families and 9 sporadic patients）. The next phenotypes were corneal dystrophy of Bowman layer （CDB） （1 family and 1 sporadic patient） and epithelial basement membrane dystrophy （EBMD） （1 sporadic patient）. Six distinct mutations responsible for TGFBI corneal dystrophies were identified in 30 individuals with corneal dystrophies. Those were, p.R124H mutation in 1 family and 2 sporadic patients with GCD, p.R555W mutation in 2 families and 3 sporadic patients with GCD, p.R124C mutation in 2 families and 7 sporadic patients with LCD, p.A620D mutation in 1 sporadic patient with LCD, p.H626R mutation in 1 sporadic patient with LCD, and p.R555Q in 1 family and 1 sporadic patient with CDB. No mutation was detected in the remaining 3 atypical GCD patients and 1 EBMD patient, CONCLUSION： GCD and LCD are the most frequent phenotypes in Chinese population. R555W was the most common mutation for GCD; R124C was the most common mutation for LCD, Our findings extend the mutational spectrum of TFGBI , and this is the extensively delineated TGFBI mutation profile associated with the various corneal dystrophies in the Chinese population.
