BACKGROUND Hypertrophic cardiomyopathy(HCM)is one of the most prevalent inherited myocardial disorders and is charac-terized by considerable genetic and phenotypic heterogeneity.A subset of patients with HCM progress ...BACKGROUND Hypertrophic cardiomyopathy(HCM)is one of the most prevalent inherited myocardial disorders and is charac-terized by considerable genetic and phenotypic heterogeneity.A subset of patients with HCM progress to a dilated phase of HCM(DPHCM),which is associated with a poor prognosis;however,the underlying pathogenesis remains inadequately understood.CASE SUMMARY In this study,we present a case involving a pedigree with familial DPHCM and conduct a retrospective review of patients with DPHCM with identified gene mutations.Through panel sequencing targeting the coding regions of 312 genes associated with inherited cardiomyopathy,a heterozygous missense mutation(c.746G>A,p.Arg249Glu)in the MYH7 gene was identified in the proband(III-5).Sanger sequencing subsequently confirmed this pathogenic mutation in three additional family members(II-4,III-4,and IV-3).A total of 26 well-documented patients with DPHCM were identified in the literature.Patients with DPHCM are commonly middle-aged and male.The mean age of patients with DPHCM was 53.43±12.79 years.Heart failure,dyspnoea,and atrial fibrillation were the most prevalent symptoms observed,accompanied by an average left ventricular end-diastolic size of 58.62 mm.CONCLUSION Our findings corroborate the pathogenicity of the MYH7(c.746G>A,p.Arg249Glu)mutation for DPHCM and suggest that the Arg249Gln mutation may be responsible for high mortality.展开更多
BACKGROUND Dystrophic epidermolysis bullosa is characterized by fragile ulcerations of the skin caused by mutations in specific genes.However,genetic typing of this con-dition is rare.CASE SUMMARY An 11-year-old femal...BACKGROUND Dystrophic epidermolysis bullosa is characterized by fragile ulcerations of the skin caused by mutations in specific genes.However,genetic typing of this con-dition is rare.CASE SUMMARY An 11-year-old female suffered from recurrent fever,visible ulcerations of the entire skin,and severe malnutrition.Genetic testing revealed a frameshift mu-tation in the coding region 4047 of the 35th intron region of COL7A1,and she was diagnosed as malnutrition-type epidermolysis bullosa.Drug therapy(immu-noglobulin,fresh frozen plasma),topical therapy(silver ion dressing),fever redu-ction,cough relief,and promotion of gastrointestinal peristalsis are mainly used for respiratory and gastrointestinal complications.The patient’s condition impro-ved after treatment.CONCLUSION Dystrophic epidermolysis bullosa caused by a new framework shift mutation in COL7A1 should be taken seriously.展开更多
BACKGROUND Maturity-onset diabetes of the young(MODY)is a monogenic form of diabetes often misdiagnosed as type 1 or type 2.The MODY7 subtype,attributed to variants in the Kruppel-like factor 11(KLF11)gene,is exceedin...BACKGROUND Maturity-onset diabetes of the young(MODY)is a monogenic form of diabetes often misdiagnosed as type 1 or type 2.The MODY7 subtype,attributed to variants in the Kruppel-like factor 11(KLF11)gene,is exceedingly rare,and its clinical spectrum is not fully characterized.Precise genetic diagnosis is essential for appropriate management but is challenging due to phenotypic overlap with other diabetes types.This case report describes a patient with a novel KLF11 variant,contributing to the understanding of this rare condition and its clinical implications.CASE SUMMARY A 50-year-old female with a family history of MODY in her son was initially diagnosed with type 2 diabetes.Due to the family history and a non-obese phenotype,a comprehensive genetic panel for monogenic diabetes was performed.The analysis identified a novel heterozygous missense variant,p.Cys105Phe,in the KLF11 gene,establishing a definitive diagnosis of MODY7.Following this diagnosis,the patient’s treatment was adjusted to include lifestyle modifications,resulting in adequate glycemic control.The patient has since maintained target glycated hemoglobin levels.CONCLUSION Monogenic diabetes type MODY7,caused by a mutation in the KLF11 gene,is extremely rare.Although some studies question its existence,compatible cases continue to be diagnosed,given its inclusion in genetic panels for MODY.展开更多
BACKGROUND IFIH1 is a protein-coding gene.Disorders associated with IFIH1 include Aicardi-Goutières syndrome(AGS)type 7 and Singleton-Merten syndrome type 1.Related pathways include RIG-I/MDA5-mediated induction ...BACKGROUND IFIH1 is a protein-coding gene.Disorders associated with IFIH1 include Aicardi-Goutières syndrome(AGS)type 7 and Singleton-Merten syndrome type 1.Related pathways include RIG-I/MDA5-mediated induction of the interferon(IFN)-α/βpathway and the innate immune system.AGS type 7 is an autosomal dominant inflammatory disorder characterized by severe neurological impairment.In infancy,most patients present with psychomotor retardation,axial hypotonia,spasticity,and brain imaging changes Laboratory assessments showed increased IFN-αactivity with upregulation of IFN signaling and IFN-stimulated gene expression.Some patients develop normally in the early stage,and then have episodic neurological deficits.CASE SUMMARY The 5-year-old girl presented with postpartum height and weight growth retardation,language retardation,brain atrophy,convulsions,and growth hormone deficiency.DNA samples were obtained from peripheral blood from the child and her parents for whole-exome sequencing and test of genome-wide copy number variation.Heterozygous mutations in the IFIH1 gene were found.Physical examination at admission found that language development was delayed,the reaction to name calling was average,there was no communication with people,but there was eye contact,no social smile,and no autonomous language.However,the child had rich gesture language and body language,could understand instructions,had bad temper.When she wants to achieve something,she starts crying or shouting.Cardiopulmonary examination showed no obvious abnormality,and abdominal examination was normal.Bilateral muscle strength and muscle tone were symmetrical and slightly decreased.Physiological reflexes exist,but pathological reflexes were not elicited.CONCLUSION We reported the clinical characteristics of a Chinese child with a clinical diagnosis of AGS type 7,which expanded the mutational spectrum of the IFIH1 gene.展开更多
BACKGROUND Antisynthetase syndrome(ASS)is characterized by the presence of antisynthetase antibodies coupled with clinical findings such as fever,polymyositis-dermatomyositis and interstitial lung disease.It is,howeve...BACKGROUND Antisynthetase syndrome(ASS)is characterized by the presence of antisynthetase antibodies coupled with clinical findings such as fever,polymyositis-dermatomyositis and interstitial lung disease.It is,however,rare to observe ASS association with B cell lymphoma presenting severe pneumonia as the first clinical manifestation.CASE SUMMARY We evaluated a 59-year-old male patient who presented with cough with sputum,shortness of breath and fever for 13 d.A chest computed tomography radiograph revealed bilateral diffuse ground-glass infiltrates in both upper fields,left lingual lobe and right middle lobe.Initially,the patient was diagnosed with severe community-acquired pneumonia and respiratory failure.He was empirically treated with broad-spectrum antibiotics,without improvement.Further analysis showed an ASS panel with anti-PL7 antibodies.Besides,electromyography evaluation demonstrated a manifestation of myogenic damage,while deltoid muscle biopsy showed irregular muscle fiber bundles especially abnormal lymphocyte infiltration.In addition,bone marrow biopsy revealed high invasive B cell lymphoma.Thus,the patient was diagnosed with a relatively rare anti–PL7 antibody positive ASS associated with B cell lymphoma.CONCLUSION This case highlights that rapidly progressive lung lesions and acute hypoxemic respiratory failure associated with heliotrope rash and extremely high lactate dehydrogenase level should be considered as the characteristics of non-infectious diseases,especially ASS and B cell lymphoma.展开更多
1 Introduction Shale formations bear abundant mineral resource and*unconventional petroleum resource,and the unconventional petroleum resource that contain in the shale formation should be integrated and researched.
Type II autosomal dominant osteopetrosis(ADO2), which is the most common form of osteopetrosis, is caused by heterozygous mutations in the chloride channel 7(CLCN7) gene. The osteopetrosis of ADO2 has been attributed ...Type II autosomal dominant osteopetrosis(ADO2), which is the most common form of osteopetrosis, is caused by heterozygous mutations in the chloride channel 7(CLCN7) gene. The osteopetrosis of ADO2 has been attributed to hypofunctional osteoclasts. The mechanism underlying the abnormality in osteoclast function remains largely unknown. This study was designed to investigate gene mutations and osteoclast function in a case that was clinically diagnosed as ADO2. Genomic DNA was extracted from blood samples of this patient, and the 25 exons of CLCN7 were amplified. Peripheral blood from the ADO2 subject and a healthy age- and sex-matched control was used to evaluate osteoclastogenesis, osteoclast morphology, and bone resorption. Analysis of DNA from the patient showed a germline heterozygous missense mutation,c.1856C>T(p.P619L), in exon 20 of CLCN7. A similar homozygous mutation at this site was previously reported in a patient with autosomal recessive osteopetrosis. When cultured, the peripheral blood mononuclear cells(PBMCs) from the ADO2 patient spontaneously differentiated into mature osteoclasts in vitro. The ADO2 patient’s PBMCs formed enhanced, but heterogeneous, osteoclasts in both the presence and absence of macrophage-colony stimulating factor, and nuclear factor-?B ligand. Bone resorption was reduced in the ADO2 patient’s osteoclasts, which exhibited aberrant morphology and abnormal distribution of integrin avβ3. Gene analysis found increased c-fos expression and reduced Rho A and integrin beta 3expression in ADO2 cells. In conclusion, our data suggest that enhanced, heterogeneous osteoclast induction may be an intrinsic characteristic of ADO2.展开更多
BACKGROUND The clinical manifestations of trisomy 7 mosaicism are diverse and nonspecific,so prenatal diagnosis is very difficult.CASE SUMMARY Two pregnant women with abnormal prenatal screening results were included....BACKGROUND The clinical manifestations of trisomy 7 mosaicism are diverse and nonspecific,so prenatal diagnosis is very difficult.CASE SUMMARY Two pregnant women with abnormal prenatal screening results were included.One was a 22-year-old woman(G1P0).At 31st week of gestation,ultrasound revealed that the posterior horn of the left lateral ventricle was 10 mm and the right renal pelvis had a separation of 7 mm.The other pregnant woman was 33 years old(G2P1L1A0),and her fetus was found to have a cardiac malformation at the 24th week of gestation.Copy number variation sequencing,whole-exome sequencing and karyotype analysis were carried out after amniocentesis,and both fetuses were diagnosed with trisomy 7 mosaicism.After parental counseling,one woman continued the pregnancy,and the other woman terminated the pregnancy.CONCLUSION In trisomy 7 mosaicism,the low proportion of trisomy does not lead to abortion,but can result in abnormal fetal development,which can be detected via ultrasound.Therefore,clinicians need to pay more attention to various aspects of fetal growth and development,combining with imaging,cellular,molecular genetics and other methods to perform comprehensive evaluations of fetuses to provide more reliable genetic counseling for pregnant women.展开更多
BACKGROUND Osteopetrosis is a family of extremely rare diseases caused by failure of osteoclasts and impaired bone resorption. Among them, autosomal dominant osteopetrosis type Ⅱ(ADO Ⅱ), related to the chloride chan...BACKGROUND Osteopetrosis is a family of extremely rare diseases caused by failure of osteoclasts and impaired bone resorption. Among them, autosomal dominant osteopetrosis type Ⅱ(ADO Ⅱ), related to the chloride channel 7(CLCN7) gene, is the most frequent form of osteopetrosis. In this study, we report a de novo mutation of CLCN7 in a patient without the family history of ADO Ⅱ.CASE SUMMARY A 5-year-old Chinese boy with ADO Ⅱ was found to have a de novo mutation in the CLCN7 gene [c.746 C>T(p.P249 L)]. Typical clinical manifestations, including thickening of the cortex of spinal bones and long bones, non-traumatic fracture of the femoral neck, and femoral head necrosis, were found in this patient. The patient is the first reported case of ADO Ⅱ with the missense mutation c.746 C>T(p.P249 L) of the CLCN7 gene reported in China. We also review the available literature on ADO Ⅱ-related CLCN7 mutations, including baseline patient clinical features, special clinical significance, and common mutations.CONCLUSION Our report will enrich the understanding of mutations in ADO Ⅱ patients. The possibility of a de novo mutation should be considered in individuals who have no family history of osteopetrosis.展开更多
BACKGROUND Human herpesvirus type 7(HHV-7)is a less common herpes virus that usually causes mild,self-limiting illnesses.However,in recent years,there have been increasing reports of HHV-7 causing serious central nerv...BACKGROUND Human herpesvirus type 7(HHV-7)is a less common herpes virus that usually causes mild,self-limiting illnesses.However,in recent years,there have been increasing reports of HHV-7 causing serious central nervous system infections,especially meningitis.The pathogenesis and clinical features of HHV-7 meningitis,particularly in adolescents with normal immune function,remain incompletely studied.Therefore,the purpose of this report is to share a case of HHV-7 meningitis in an immunocompetent adolescent with a view to deepening our understanding of the disease.CASE SUMMARY A 12-year-old female was admitted with fever,headache,and vomiting.4 d before admission,the patient developed a fever without obvious induction,with a temperature up to 39.5℃,no convulsions,accompanied by chills,headaches,fatigue,and no muscle aches.The patient was treated with fever reduction,which could be reduced to 38℃;repeated high fever,accompanied by vomiting 7-8 times;and no abdominal pain or diarrhea.The patient was diagnosed with"acute suppurative tonsillitis"in a local hospital,and the blood routine was generally normal.The patient was given symptomatic support treatment such as"ceftriaxone sodium"and antiemetic rehydration for 2 d,and his condition did not improve.The patient's physical examination showed pharyngeal congestion,bilateral tonsil grade I hypertrophy,regression of purulent secretions,and cervical resistance.Ocular B-ultrasound:Opacity of the vitreous body and edema of the optic disc in both eyes.Optical coherence tomography examination showed that the macular fovea was generally normal in both eyes,with edema of the optic disc.DNA virus monitoring results:HHV-7.We gave ganciclovir antiviral therapy,dexamethasone anti-inflammatory treatment,mannitol to reduce cranial pressure,omeprazole to protect gastrointestinal mucosa,and calcium and potassium supplementation.CONCLUSION This study reports a case of HHV-7 meningitis in an adolescent with normal immune function.Through comprehensive analysis of the clinical manifestations,laboratory tests,and treatment methods of the patient,it is found that early identification and antiviral treatment are essential for the outcome of the disease.This case suggests that despite normal immune function,adolescents may still suffer from herpes virus type 7 meningitis,so clinicians should be vigilant and take effective treatment measures in time.展开更多
Spinal muscular atrophy(SMA)is an autosomal recessive hereditary neuromuscular disease.Exon 7 and 8 of survival of motor neuron 1(SMN1)gene or only exon 7 homology deletion leads to the failure to produce a full-lengt...Spinal muscular atrophy(SMA)is an autosomal recessive hereditary neuromuscular disease.Exon 7 and 8 of survival of motor neuron 1(SMN1)gene or only exon 7 homology deletion leads to the failure to produce a full-length SMN gene.The copy number of SMN2 gene with high homology of SMN1 affects the degree of disease and was the target gene for targeting therapy,in which splicing silencer in intron 7 was the key to suppress the inclusion of exon 7.In this study,we projected to use CRISPR/Case 9 for the targeted editing of intronic-splicing silencer(ISS)sequence to promote the inclusion of SMN2 exon 7 and increase the production of SMN2 full-length(FL)gene expression.It happens that there was a protospacer adjacent motif(PAM)at one end of the ISS sequence according to the design of sgRNA.The recombinant vector of sgRNA HSMN2 CRISPR/Case 9 was constructed and transfected into HEK293 cells.Sequencing results showed that the ISS sequence could be edited accurately and targeting in the predicted direction,in which deleting small fragments,inserting small amounts and mutation.Quantitative analysis of RT-PCR products by restriction enzyme of DdeI digestion showed that the FL of SMN2 increased by 8%(P<0.05).In the primary cultured chondrocytes of SMA mice,in which sgRNA HSMN2 CRISPR/Case9 recombinant vector transfection could increase the SMN2 FL gene by 23%(P<0.05)and significantly improve SMN protein levels(P<0.05).CRISPR/Case 9 is an effective tool for gene editing and therapy of hereditary diseases,but it is rarely reported in the treatment of SMA diseases.This study shows that CRISPR/Case 9 was first used for the precision target of ISS sequence editing,which can effectively promote the production of SMN2 FL gene expressions,in which there was an important clinical reference value.展开更多
BACKGROUND Spinocerebellar ataxia recessive type 7(SCAR7)is a rare clinical manifestation beginning in childhood or adolescence.SCAR7 is caused by tripeptidyl peptidase 1(TPP1)gene mutations,and presents with cerebell...BACKGROUND Spinocerebellar ataxia recessive type 7(SCAR7)is a rare clinical manifestation beginning in childhood or adolescence.SCAR7 is caused by tripeptidyl peptidase 1(TPP1)gene mutations,and presents with cerebellar ataxia,pyramidal signs,neurocognitive impairment,deep paresthesia,and cerebellar atrophy.CASE SUMMARY Here,we describe a 25-year-old female patient in China who presented with increasing difficulty walking,falling easily,shaking limbs,instability holding items,slurred speech,coughing when drinking,palpitations,and frequent hunger and overeating.Magnetic resonance imaging showed cerebellar atrophy.Whole exome sequencing detected two compound heterozygous mutations in the TPP1 gene:c.1468G>A p.Glu490Lys and c.1417G>A p.Gly473Arg.Considering the patient’s clinical presentation and genetic test results,we hypothesized that complex heterozygous mutations cause TPP1 enzyme deficiency,which may lead to SCAR7.CONCLUSION We report the first case of SCAR7 from China.We also identify novel compound heterozygous mutations in the TPP1 gene associated with SCAR7,expanding the range of known disease-causing mutations for SCAR7.展开更多
The Toroidal Field (TF) coil case of the HT-7U superconducting tokamak device is made of austenitic stainless steel 316LN and is designed to operate at cryogenic temperature (4 K). 316LN can retain high strength and f...The Toroidal Field (TF) coil case of the HT-7U superconducting tokamak device is made of austenitic stainless steel 316LN and is designed to operate at cryogenic temperature (4 K). 316LN can retain high strength and fracture toughness at 4 K. Feasibility study on technical process of welding has been experimentally considered as a hopeful joint method for suppression of post-welding deformation and reduction of over-heating. Meanwhile the final range of stress intensity and the stress intensity factor (K) for pre-cracks of welding structure have been determined by using J-integral. These related results are optimistic and have shown that there's no problem in strength and fracture toughness at the vicinity of the pre-crack tip. This paper introduces the welding structure of TF coil case in detail.展开更多
Background:Human herpesvirus(HHV)-7 is usually associated with febrile seizures.Later onset and higher frequency of seizures are characteristic of pediatric HHV-7,compared with HHV-6 infection.The HHV-7-related severe...Background:Human herpesvirus(HHV)-7 is usually associated with febrile seizures.Later onset and higher frequency of seizures are characteristic of pediatric HHV-7,compared with HHV-6 infection.The HHV-7-related severe neurological disorders are predominantly observed in immunocompromised individuals.Reports of healthy individuals with HHV-7 infection and diverse neurological disorders are limited.Patient Description:We present a case of HHV-7-related epilepsy in an immunocompetent 11-year old boy and extensive infectious and autoimmune testing positive only for HHV-7 in the cerebrospinal fluid.The patient made a good recovery after treatment with intravenous immunoglobulin and methylprednisolone.Discussion:This is the first reported case of epilepsy associated with HHV-7 in a previously healthy individual.It also demonstrates that intravenous immunoglobulin and steroids may be used in the course of this disorder and may be beneficial for recovery.展开更多
BACKGROUND Variants in the MYO7A gene commonly result in Usher syndrome,and in rare cases lead to autosomal dominant non-syndromic deafness(DFNA11).Currently,only nine variants have been reported to be responsible for...BACKGROUND Variants in the MYO7A gene commonly result in Usher syndrome,and in rare cases lead to autosomal dominant non-syndromic deafness(DFNA11).Currently,only nine variants have been reported to be responsible for DFNA11 and their clinical phenotypes are not identical.Here we present a novel variant causing DFNA11 identified in a three-generation Chinese family.CASE SUMMARY The proband was a 53-year-old Han male who presented with post-lingual bilateral symmetrical moderate sensorineural hearing loss.We learned from the patient’s medical history collection that multiple family members also had similar hearing loss,generally occurring around the age of 40.Subsequent investigation by high-throughput sequencing identified a novel MYO7A variant.To provide evidence supporting that this variant is responsible for the hearing loss in the studied family,we performed Sanger sequencing on 11 family members and found that the variant co-segregated with the deafness phenotype.In addition,the clinical manifestation of the 11 affected family members was found to be lateonset bilateral slowly progressive hearing loss,inherited in this family in an autosomal dominant manner.None of the affected family members had visual impairment or vestibular symptoms;therefore,we believe that this novel MYO7A variant is responsible for the rare DFNA11 in this family.CONCLUSION We report a novel variant leading to DFNA11 which further enriches the collection of MYO7A variants,and our review of the nine previous variants that have been identified to cause DFNA11 provides a reference for clinical genetic counseling.展开更多
目的系统评价趋化因子受体7(chemokine factor receptor 7,CXCR7)在胃癌组织中的表达及其临床意义.方法检索Pub Med、EMBASE、Web of Science、C N K I、C B M、维普和万方数据库关于C X C R7在胃癌中表达的病例对照研究.结果用Rev Man...目的系统评价趋化因子受体7(chemokine factor receptor 7,CXCR7)在胃癌组织中的表达及其临床意义.方法检索Pub Med、EMBASE、Web of Science、C N K I、C B M、维普和万方数据库关于C X C R7在胃癌中表达的病例对照研究.结果用Rev Man5.3对比值比(odds ratio,OR)及95%置信区间(confidence interval,CI)进行统计分析.结果共纳入4个病例对照研究,共425个病例,胃癌组320例,正常对照组105例.Meta分析结果显示:CXCR7在胃癌组织中呈高表达(OR=46.35,95%CI:19.99-107.43).并且CXCR7的表达与胃癌组织的浸润深度(OR=0.17,95%CI:0.05-0.58)、淋巴结转移(OR=0.23,95%C I:0.12-0.44)、临床分期(O R=0.29,95%CI:0.16-0.54)有关.至于CXCR7是否影响胃癌组织的分化,目前尚不能确定,需要更多的研究来明确、证实.结论胃癌组织中CXCR7的表达高于正常组织.C X C R7在胃癌组织中的表达与胃癌的浸润深度、淋巴结转移和临床分期有关,说明CXCR7在胃癌的发展、转移中发挥作用.展开更多
目的观察双相躁狂患者血浆中GRM-7 m RNA的表达水平的改变及与双相躁狂之间的关系。方法将105例双相障碍躁狂发作患者设为患者组,100例与患者组在年龄和性别上匹配的健康志愿者设为对照组。患者组常规应用碳酸锂治疗,观察1个月,患者组...目的观察双相躁狂患者血浆中GRM-7 m RNA的表达水平的改变及与双相躁狂之间的关系。方法将105例双相障碍躁狂发作患者设为患者组,100例与患者组在年龄和性别上匹配的健康志愿者设为对照组。患者组常规应用碳酸锂治疗,观察1个月,患者组于入组时和治疗1个月时、对照组于入组时,分别评定BRMS量表并收集血浆,采用实时荧光定量PCR技术检测GRM-7 m RNA的表达水平,最后对检测结果及BRMS评分进行统计分析。结果患者组血浆GRM-7 m RNA表达显著低于对照组(P<0.001);治疗1个月后,患者组血浆GRM-7m RNA的表达水平显著升高(P<0.001)。结论血浆GRM-7 m RNA的表达水平和双相障碍躁狂发作有关。展开更多
基金Supported by National Natural Science Foundation of China,No.81770379.
文摘BACKGROUND Hypertrophic cardiomyopathy(HCM)is one of the most prevalent inherited myocardial disorders and is charac-terized by considerable genetic and phenotypic heterogeneity.A subset of patients with HCM progress to a dilated phase of HCM(DPHCM),which is associated with a poor prognosis;however,the underlying pathogenesis remains inadequately understood.CASE SUMMARY In this study,we present a case involving a pedigree with familial DPHCM and conduct a retrospective review of patients with DPHCM with identified gene mutations.Through panel sequencing targeting the coding regions of 312 genes associated with inherited cardiomyopathy,a heterozygous missense mutation(c.746G>A,p.Arg249Glu)in the MYH7 gene was identified in the proband(III-5).Sanger sequencing subsequently confirmed this pathogenic mutation in three additional family members(II-4,III-4,and IV-3).A total of 26 well-documented patients with DPHCM were identified in the literature.Patients with DPHCM are commonly middle-aged and male.The mean age of patients with DPHCM was 53.43±12.79 years.Heart failure,dyspnoea,and atrial fibrillation were the most prevalent symptoms observed,accompanied by an average left ventricular end-diastolic size of 58.62 mm.CONCLUSION Our findings corroborate the pathogenicity of the MYH7(c.746G>A,p.Arg249Glu)mutation for DPHCM and suggest that the Arg249Gln mutation may be responsible for high mortality.
文摘BACKGROUND Dystrophic epidermolysis bullosa is characterized by fragile ulcerations of the skin caused by mutations in specific genes.However,genetic typing of this con-dition is rare.CASE SUMMARY An 11-year-old female suffered from recurrent fever,visible ulcerations of the entire skin,and severe malnutrition.Genetic testing revealed a frameshift mu-tation in the coding region 4047 of the 35th intron region of COL7A1,and she was diagnosed as malnutrition-type epidermolysis bullosa.Drug therapy(immu-noglobulin,fresh frozen plasma),topical therapy(silver ion dressing),fever redu-ction,cough relief,and promotion of gastrointestinal peristalsis are mainly used for respiratory and gastrointestinal complications.The patient’s condition impro-ved after treatment.CONCLUSION Dystrophic epidermolysis bullosa caused by a new framework shift mutation in COL7A1 should be taken seriously.
文摘BACKGROUND Maturity-onset diabetes of the young(MODY)is a monogenic form of diabetes often misdiagnosed as type 1 or type 2.The MODY7 subtype,attributed to variants in the Kruppel-like factor 11(KLF11)gene,is exceedingly rare,and its clinical spectrum is not fully characterized.Precise genetic diagnosis is essential for appropriate management but is challenging due to phenotypic overlap with other diabetes types.This case report describes a patient with a novel KLF11 variant,contributing to the understanding of this rare condition and its clinical implications.CASE SUMMARY A 50-year-old female with a family history of MODY in her son was initially diagnosed with type 2 diabetes.Due to the family history and a non-obese phenotype,a comprehensive genetic panel for monogenic diabetes was performed.The analysis identified a novel heterozygous missense variant,p.Cys105Phe,in the KLF11 gene,establishing a definitive diagnosis of MODY7.Following this diagnosis,the patient’s treatment was adjusted to include lifestyle modifications,resulting in adequate glycemic control.The patient has since maintained target glycated hemoglobin levels.CONCLUSION Monogenic diabetes type MODY7,caused by a mutation in the KLF11 gene,is extremely rare.Although some studies question its existence,compatible cases continue to be diagnosed,given its inclusion in genetic panels for MODY.
文摘BACKGROUND IFIH1 is a protein-coding gene.Disorders associated with IFIH1 include Aicardi-Goutières syndrome(AGS)type 7 and Singleton-Merten syndrome type 1.Related pathways include RIG-I/MDA5-mediated induction of the interferon(IFN)-α/βpathway and the innate immune system.AGS type 7 is an autosomal dominant inflammatory disorder characterized by severe neurological impairment.In infancy,most patients present with psychomotor retardation,axial hypotonia,spasticity,and brain imaging changes Laboratory assessments showed increased IFN-αactivity with upregulation of IFN signaling and IFN-stimulated gene expression.Some patients develop normally in the early stage,and then have episodic neurological deficits.CASE SUMMARY The 5-year-old girl presented with postpartum height and weight growth retardation,language retardation,brain atrophy,convulsions,and growth hormone deficiency.DNA samples were obtained from peripheral blood from the child and her parents for whole-exome sequencing and test of genome-wide copy number variation.Heterozygous mutations in the IFIH1 gene were found.Physical examination at admission found that language development was delayed,the reaction to name calling was average,there was no communication with people,but there was eye contact,no social smile,and no autonomous language.However,the child had rich gesture language and body language,could understand instructions,had bad temper.When she wants to achieve something,she starts crying or shouting.Cardiopulmonary examination showed no obvious abnormality,and abdominal examination was normal.Bilateral muscle strength and muscle tone were symmetrical and slightly decreased.Physiological reflexes exist,but pathological reflexes were not elicited.CONCLUSION We reported the clinical characteristics of a Chinese child with a clinical diagnosis of AGS type 7,which expanded the mutational spectrum of the IFIH1 gene.
基金Supported by National Natural Science Foundation of China,No.81900020Natural Science Foundation of Zhejiang Province,China,No.LQ19H160020.
文摘BACKGROUND Antisynthetase syndrome(ASS)is characterized by the presence of antisynthetase antibodies coupled with clinical findings such as fever,polymyositis-dermatomyositis and interstitial lung disease.It is,however,rare to observe ASS association with B cell lymphoma presenting severe pneumonia as the first clinical manifestation.CASE SUMMARY We evaluated a 59-year-old male patient who presented with cough with sputum,shortness of breath and fever for 13 d.A chest computed tomography radiograph revealed bilateral diffuse ground-glass infiltrates in both upper fields,left lingual lobe and right middle lobe.Initially,the patient was diagnosed with severe community-acquired pneumonia and respiratory failure.He was empirically treated with broad-spectrum antibiotics,without improvement.Further analysis showed an ASS panel with anti-PL7 antibodies.Besides,electromyography evaluation demonstrated a manifestation of myogenic damage,while deltoid muscle biopsy showed irregular muscle fiber bundles especially abnormal lymphocyte infiltration.In addition,bone marrow biopsy revealed high invasive B cell lymphoma.Thus,the patient was diagnosed with a relatively rare anti–PL7 antibody positive ASS associated with B cell lymphoma.CONCLUSION This case highlights that rapidly progressive lung lesions and acute hypoxemic respiratory failure associated with heliotrope rash and extremely high lactate dehydrogenase level should be considered as the characteristics of non-infectious diseases,especially ASS and B cell lymphoma.
基金supported by funding the National Basic Research Program of China (973 Program) and the grant number is 2014CB239000
文摘1 Introduction Shale formations bear abundant mineral resource and*unconventional petroleum resource,and the unconventional petroleum resource that contain in the shale formation should be integrated and researched.
基金supported by grants from the National Natural Science Foundation of China(Nos.81572639,81370969 and 81072190 to X Yu)the Ministry of Education of the People's Republic of China(No.20130181110066 to X Yu)the Chengdu Bureau of Science and Technology(No.2014-HM01-00382-SF to X Yu)
文摘Type II autosomal dominant osteopetrosis(ADO2), which is the most common form of osteopetrosis, is caused by heterozygous mutations in the chloride channel 7(CLCN7) gene. The osteopetrosis of ADO2 has been attributed to hypofunctional osteoclasts. The mechanism underlying the abnormality in osteoclast function remains largely unknown. This study was designed to investigate gene mutations and osteoclast function in a case that was clinically diagnosed as ADO2. Genomic DNA was extracted from blood samples of this patient, and the 25 exons of CLCN7 were amplified. Peripheral blood from the ADO2 subject and a healthy age- and sex-matched control was used to evaluate osteoclastogenesis, osteoclast morphology, and bone resorption. Analysis of DNA from the patient showed a germline heterozygous missense mutation,c.1856C>T(p.P619L), in exon 20 of CLCN7. A similar homozygous mutation at this site was previously reported in a patient with autosomal recessive osteopetrosis. When cultured, the peripheral blood mononuclear cells(PBMCs) from the ADO2 patient spontaneously differentiated into mature osteoclasts in vitro. The ADO2 patient’s PBMCs formed enhanced, but heterogeneous, osteoclasts in both the presence and absence of macrophage-colony stimulating factor, and nuclear factor-?B ligand. Bone resorption was reduced in the ADO2 patient’s osteoclasts, which exhibited aberrant morphology and abnormal distribution of integrin avβ3. Gene analysis found increased c-fos expression and reduced Rho A and integrin beta 3expression in ADO2 cells. In conclusion, our data suggest that enhanced, heterogeneous osteoclast induction may be an intrinsic characteristic of ADO2.
文摘BACKGROUND The clinical manifestations of trisomy 7 mosaicism are diverse and nonspecific,so prenatal diagnosis is very difficult.CASE SUMMARY Two pregnant women with abnormal prenatal screening results were included.One was a 22-year-old woman(G1P0).At 31st week of gestation,ultrasound revealed that the posterior horn of the left lateral ventricle was 10 mm and the right renal pelvis had a separation of 7 mm.The other pregnant woman was 33 years old(G2P1L1A0),and her fetus was found to have a cardiac malformation at the 24th week of gestation.Copy number variation sequencing,whole-exome sequencing and karyotype analysis were carried out after amniocentesis,and both fetuses were diagnosed with trisomy 7 mosaicism.After parental counseling,one woman continued the pregnancy,and the other woman terminated the pregnancy.CONCLUSION In trisomy 7 mosaicism,the low proportion of trisomy does not lead to abortion,but can result in abnormal fetal development,which can be detected via ultrasound.Therefore,clinicians need to pay more attention to various aspects of fetal growth and development,combining with imaging,cellular,molecular genetics and other methods to perform comprehensive evaluations of fetuses to provide more reliable genetic counseling for pregnant women.
文摘BACKGROUND Osteopetrosis is a family of extremely rare diseases caused by failure of osteoclasts and impaired bone resorption. Among them, autosomal dominant osteopetrosis type Ⅱ(ADO Ⅱ), related to the chloride channel 7(CLCN7) gene, is the most frequent form of osteopetrosis. In this study, we report a de novo mutation of CLCN7 in a patient without the family history of ADO Ⅱ.CASE SUMMARY A 5-year-old Chinese boy with ADO Ⅱ was found to have a de novo mutation in the CLCN7 gene [c.746 C>T(p.P249 L)]. Typical clinical manifestations, including thickening of the cortex of spinal bones and long bones, non-traumatic fracture of the femoral neck, and femoral head necrosis, were found in this patient. The patient is the first reported case of ADO Ⅱ with the missense mutation c.746 C>T(p.P249 L) of the CLCN7 gene reported in China. We also review the available literature on ADO Ⅱ-related CLCN7 mutations, including baseline patient clinical features, special clinical significance, and common mutations.CONCLUSION Our report will enrich the understanding of mutations in ADO Ⅱ patients. The possibility of a de novo mutation should be considered in individuals who have no family history of osteopetrosis.
文摘BACKGROUND Human herpesvirus type 7(HHV-7)is a less common herpes virus that usually causes mild,self-limiting illnesses.However,in recent years,there have been increasing reports of HHV-7 causing serious central nervous system infections,especially meningitis.The pathogenesis and clinical features of HHV-7 meningitis,particularly in adolescents with normal immune function,remain incompletely studied.Therefore,the purpose of this report is to share a case of HHV-7 meningitis in an immunocompetent adolescent with a view to deepening our understanding of the disease.CASE SUMMARY A 12-year-old female was admitted with fever,headache,and vomiting.4 d before admission,the patient developed a fever without obvious induction,with a temperature up to 39.5℃,no convulsions,accompanied by chills,headaches,fatigue,and no muscle aches.The patient was treated with fever reduction,which could be reduced to 38℃;repeated high fever,accompanied by vomiting 7-8 times;and no abdominal pain or diarrhea.The patient was diagnosed with"acute suppurative tonsillitis"in a local hospital,and the blood routine was generally normal.The patient was given symptomatic support treatment such as"ceftriaxone sodium"and antiemetic rehydration for 2 d,and his condition did not improve.The patient's physical examination showed pharyngeal congestion,bilateral tonsil grade I hypertrophy,regression of purulent secretions,and cervical resistance.Ocular B-ultrasound:Opacity of the vitreous body and edema of the optic disc in both eyes.Optical coherence tomography examination showed that the macular fovea was generally normal in both eyes,with edema of the optic disc.DNA virus monitoring results:HHV-7.We gave ganciclovir antiviral therapy,dexamethasone anti-inflammatory treatment,mannitol to reduce cranial pressure,omeprazole to protect gastrointestinal mucosa,and calcium and potassium supplementation.CONCLUSION This study reports a case of HHV-7 meningitis in an adolescent with normal immune function.Through comprehensive analysis of the clinical manifestations,laboratory tests,and treatment methods of the patient,it is found that early identification and antiviral treatment are essential for the outcome of the disease.This case suggests that despite normal immune function,adolescents may still suffer from herpes virus type 7 meningitis,so clinicians should be vigilant and take effective treatment measures in time.
基金Nantong Science and Technology Program,grant number(JC2018090)the Practice Innovation Training Program Projects for the Jiangsu College Students,grant number(201810304028z)the Scientific Innovation Research of College Graduates in Jiangsu Province,grant number(KYCX18-2415)。
文摘Spinal muscular atrophy(SMA)is an autosomal recessive hereditary neuromuscular disease.Exon 7 and 8 of survival of motor neuron 1(SMN1)gene or only exon 7 homology deletion leads to the failure to produce a full-length SMN gene.The copy number of SMN2 gene with high homology of SMN1 affects the degree of disease and was the target gene for targeting therapy,in which splicing silencer in intron 7 was the key to suppress the inclusion of exon 7.In this study,we projected to use CRISPR/Case 9 for the targeted editing of intronic-splicing silencer(ISS)sequence to promote the inclusion of SMN2 exon 7 and increase the production of SMN2 full-length(FL)gene expression.It happens that there was a protospacer adjacent motif(PAM)at one end of the ISS sequence according to the design of sgRNA.The recombinant vector of sgRNA HSMN2 CRISPR/Case 9 was constructed and transfected into HEK293 cells.Sequencing results showed that the ISS sequence could be edited accurately and targeting in the predicted direction,in which deleting small fragments,inserting small amounts and mutation.Quantitative analysis of RT-PCR products by restriction enzyme of DdeI digestion showed that the FL of SMN2 increased by 8%(P<0.05).In the primary cultured chondrocytes of SMA mice,in which sgRNA HSMN2 CRISPR/Case9 recombinant vector transfection could increase the SMN2 FL gene by 23%(P<0.05)and significantly improve SMN protein levels(P<0.05).CRISPR/Case 9 is an effective tool for gene editing and therapy of hereditary diseases,but it is rarely reported in the treatment of SMA diseases.This study shows that CRISPR/Case 9 was first used for the precision target of ISS sequence editing,which can effectively promote the production of SMN2 FL gene expressions,in which there was an important clinical reference value.
基金Supported by Postdoctoral program of the Affiliated Hospital of Jining Medical University,No.JYFY303573Health Commission of Shandong Province,No.202006010928+1 种基金Academician Lin He New Medicine in Jining Medical University,No.JYHL2018FMS05Affiliated Hospital of Jining Medical University,No.2018-BS-004.
文摘BACKGROUND Spinocerebellar ataxia recessive type 7(SCAR7)is a rare clinical manifestation beginning in childhood or adolescence.SCAR7 is caused by tripeptidyl peptidase 1(TPP1)gene mutations,and presents with cerebellar ataxia,pyramidal signs,neurocognitive impairment,deep paresthesia,and cerebellar atrophy.CASE SUMMARY Here,we describe a 25-year-old female patient in China who presented with increasing difficulty walking,falling easily,shaking limbs,instability holding items,slurred speech,coughing when drinking,palpitations,and frequent hunger and overeating.Magnetic resonance imaging showed cerebellar atrophy.Whole exome sequencing detected two compound heterozygous mutations in the TPP1 gene:c.1468G>A p.Glu490Lys and c.1417G>A p.Gly473Arg.Considering the patient’s clinical presentation and genetic test results,we hypothesized that complex heterozygous mutations cause TPP1 enzyme deficiency,which may lead to SCAR7.CONCLUSION We report the first case of SCAR7 from China.We also identify novel compound heterozygous mutations in the TPP1 gene associated with SCAR7,expanding the range of known disease-causing mutations for SCAR7.
文摘The Toroidal Field (TF) coil case of the HT-7U superconducting tokamak device is made of austenitic stainless steel 316LN and is designed to operate at cryogenic temperature (4 K). 316LN can retain high strength and fracture toughness at 4 K. Feasibility study on technical process of welding has been experimentally considered as a hopeful joint method for suppression of post-welding deformation and reduction of over-heating. Meanwhile the final range of stress intensity and the stress intensity factor (K) for pre-cracks of welding structure have been determined by using J-integral. These related results are optimistic and have shown that there's no problem in strength and fracture toughness at the vicinity of the pre-crack tip. This paper introduces the welding structure of TF coil case in detail.
文摘Background:Human herpesvirus(HHV)-7 is usually associated with febrile seizures.Later onset and higher frequency of seizures are characteristic of pediatric HHV-7,compared with HHV-6 infection.The HHV-7-related severe neurological disorders are predominantly observed in immunocompromised individuals.Reports of healthy individuals with HHV-7 infection and diverse neurological disorders are limited.Patient Description:We present a case of HHV-7-related epilepsy in an immunocompetent 11-year old boy and extensive infectious and autoimmune testing positive only for HHV-7 in the cerebrospinal fluid.The patient made a good recovery after treatment with intravenous immunoglobulin and methylprednisolone.Discussion:This is the first reported case of epilepsy associated with HHV-7 in a previously healthy individual.It also demonstrates that intravenous immunoglobulin and steroids may be used in the course of this disorder and may be beneficial for recovery.
文摘BACKGROUND Variants in the MYO7A gene commonly result in Usher syndrome,and in rare cases lead to autosomal dominant non-syndromic deafness(DFNA11).Currently,only nine variants have been reported to be responsible for DFNA11 and their clinical phenotypes are not identical.Here we present a novel variant causing DFNA11 identified in a three-generation Chinese family.CASE SUMMARY The proband was a 53-year-old Han male who presented with post-lingual bilateral symmetrical moderate sensorineural hearing loss.We learned from the patient’s medical history collection that multiple family members also had similar hearing loss,generally occurring around the age of 40.Subsequent investigation by high-throughput sequencing identified a novel MYO7A variant.To provide evidence supporting that this variant is responsible for the hearing loss in the studied family,we performed Sanger sequencing on 11 family members and found that the variant co-segregated with the deafness phenotype.In addition,the clinical manifestation of the 11 affected family members was found to be lateonset bilateral slowly progressive hearing loss,inherited in this family in an autosomal dominant manner.None of the affected family members had visual impairment or vestibular symptoms;therefore,we believe that this novel MYO7A variant is responsible for the rare DFNA11 in this family.CONCLUSION We report a novel variant leading to DFNA11 which further enriches the collection of MYO7A variants,and our review of the nine previous variants that have been identified to cause DFNA11 provides a reference for clinical genetic counseling.
文摘目的系统评价趋化因子受体7(chemokine factor receptor 7,CXCR7)在胃癌组织中的表达及其临床意义.方法检索Pub Med、EMBASE、Web of Science、C N K I、C B M、维普和万方数据库关于C X C R7在胃癌中表达的病例对照研究.结果用Rev Man5.3对比值比(odds ratio,OR)及95%置信区间(confidence interval,CI)进行统计分析.结果共纳入4个病例对照研究,共425个病例,胃癌组320例,正常对照组105例.Meta分析结果显示:CXCR7在胃癌组织中呈高表达(OR=46.35,95%CI:19.99-107.43).并且CXCR7的表达与胃癌组织的浸润深度(OR=0.17,95%CI:0.05-0.58)、淋巴结转移(OR=0.23,95%C I:0.12-0.44)、临床分期(O R=0.29,95%CI:0.16-0.54)有关.至于CXCR7是否影响胃癌组织的分化,目前尚不能确定,需要更多的研究来明确、证实.结论胃癌组织中CXCR7的表达高于正常组织.C X C R7在胃癌组织中的表达与胃癌的浸润深度、淋巴结转移和临床分期有关,说明CXCR7在胃癌的发展、转移中发挥作用.
文摘目的观察双相躁狂患者血浆中GRM-7 m RNA的表达水平的改变及与双相躁狂之间的关系。方法将105例双相障碍躁狂发作患者设为患者组,100例与患者组在年龄和性别上匹配的健康志愿者设为对照组。患者组常规应用碳酸锂治疗,观察1个月,患者组于入组时和治疗1个月时、对照组于入组时,分别评定BRMS量表并收集血浆,采用实时荧光定量PCR技术检测GRM-7 m RNA的表达水平,最后对检测结果及BRMS评分进行统计分析。结果患者组血浆GRM-7 m RNA表达显著低于对照组(P<0.001);治疗1个月后,患者组血浆GRM-7m RNA的表达水平显著升高(P<0.001)。结论血浆GRM-7 m RNA的表达水平和双相障碍躁狂发作有关。
