AIM:To identify a maculopathy patient caused by new recessive compound heterozygous variants in RP1L1.METHODS:Comprehensive retinal morphological and functional examinations were evaluated for the patient with RP1L1 m...AIM:To identify a maculopathy patient caused by new recessive compound heterozygous variants in RP1L1.METHODS:Comprehensive retinal morphological and functional examinations were evaluated for the patient with RP1L1 maculopathy.Targeted sequence capture array technique was used to screen potential pathologic variants.Polymerase chain reaction and Sanger sequencing were used to confirm the screening results.RESULTS:Fundus examination showed round macular lesions appeared in both eyes.Optical coherence tomography showed that the inner segment/outer segment continuity was disorganized and disruptive in the left eye,but it was uneven and slightly elevated in the right eye.Fundus autofluorescence showed patchy hyper-autofluorescence in the macula.Visual field examination indicates central defects in both eyes.Electroretinogram(ERG)and multifocal ERG showed no obvious abnormalities.Fundus fluorescein angiography in the macula showed obviously irregular hyper-fluorescence in the right eye and slightly hyper-fluorescence in the left eye.We found that the proband carried a missense variant(c.1972C>T)and a deletion variant(c.4717_4718del)of RP1L1,which were originated from the parents and formed compound heterozygous variants.Both variants are likely pathogenic according to the ACMG criteria.Multimodal imaging,ERG and detailed medical history are important diagnostic tools for differentiating between acquired and inherited retinal disorders.CONCLUSION:A maculopathy case with detailed retinal phenotype and new recessive compound heterozygous variants of RP1L1 is identified in a Chinese family,which expands the understanding of phenotype and genotype in RP1L1 maculopathy.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
Protein C(PC)is an important physiological anticoagulant protein that is a vitamin K-dependent serine protease precursor that is synthesized mainly by the liver and released into the blood.It is activated by the throm...Protein C(PC)is an important physiological anticoagulant protein that is a vitamin K-dependent serine protease precursor that is synthesized mainly by the liver and released into the blood.It is activated by the thrombin/thrombomodulin complex to form activated protein C(APC),which exerts physiological anticoagulant functions by inactivating activated coagulation factors Ⅴ and Ⅷ.1 PC is encoded by the protein C gene(PROC),which is located in the q13-q14 region of chromosome 2 and consists of 9 exons and 8 introns and is approximately 11.2 kb in length.2 Individuals carrying the PROC gene variant have a risk of developing venous thrombosis that is approximately 7 times greater than that of normal individuals.PC deficiency caused by homozygous or compound heterozygous variations in the PROC gene is extremely rare.3 The prevalence rate of protein C deficiency among healthy people in China is approximately 0.29%.4 Here,we report a teenage patient with multiple recurrent deep venous thromboses associated with protein C deficiency caused by compound heterozygous variants that have not been previously reported.展开更多
Titin,the largest known protein in nature,is a giant sarcomeric protein that plays essential architectural,developmental,and regulatory roles in striated muscles.Mutations in the TTN gene(MIM:188840)that encodes titin...Titin,the largest known protein in nature,is a giant sarcomeric protein that plays essential architectural,developmental,and regulatory roles in striated muscles.Mutations in the TTN gene(MIM:188840)that encodes titin are related to a broad range of muscle diseases known as titinopathies,with diverse clinical manifestations including weakness,contractures,scoliosis,respiratory failure,and cardiomyopathy.1 In this case report,we describe two sisters with severe scoliosis,both carrying novel compound heterozygous variants in the TTN gene,yet presenting distinct clinical phenotypes,adding to the growing body of evidence linking TTN mutations to scoliosis and other titinrelated disorders.展开更多
Objective:Glucose-6-phosphate isomerase(GPI)deficiency is a rare hereditary nonspherocytic hemolytic anemia caused by GPI gene variants.This disorder exhibits wide heterogeneity in its clinical manifestations and mole...Objective:Glucose-6-phosphate isomerase(GPI)deficiency is a rare hereditary nonspherocytic hemolytic anemia caused by GPI gene variants.This disorder exhibits wide heterogeneity in its clinical manifestations and molecular characteristics,often posing challenges for precise diagnoses using conventional methods.To this end,this study aimed to identify the novel variants responsible for GPI deficiency in a Chinese family.Methods:The clinical manifestations of the patient were summarized and analyzed for GPI deficiency phenotype diagnosis.Novel compound heterozygous variants of the GPI gene,c.174C>A(p.Asn58Lys)and c.1538G>T(p.Trp513Leu),were identified using whole-exome and Sanger sequencing.The AlphaFold program and Chimera software were used to analyze the effects of compound heterozygous variants on GPI structure.Results:By characterizing 53 GPI missense/nonsense variants from previous literature and two novel missense variants identified in this study,we found that most variants were located in exons 3,4,12,and 18,with a few localized in exons 8,9,and 14.This study identified novel compound heterozygous variants associated with GPI deficiency.These pathogenic variants disrupt hydrogen bonds formed by highly conserved GPI amino acids.Conclusion:Early family-based sequencing analyses,especially for patients with congenital anemia,can help increase diagnostic accuracy for GPI deficiency,improve child healthcare,and enable genetic counseling.展开更多
Objective To analyze the clinical phenotypes and genetic features of a child with developmental and epileptic encephalopathy due to compound heterozygous variants in the ALG14 gene,and to improve clinicians'unders...Objective To analyze the clinical phenotypes and genetic features of a child with developmental and epileptic encephalopathy due to compound heterozygous variants in the ALG14 gene,and to improve clinicians'understanding of the ALG14 gene and its associated disorders.展开更多
基金Supported by Shenzhen Science and Technology Program,Shenzhen,China(No.JCYJ20200109145001814,No.SGDX20211123120001001)the National Natural Science Foundation of China(No.81970790)Sanming Project of Medicine in Shenzhen(No.SZSM202011015).
文摘AIM:To identify a maculopathy patient caused by new recessive compound heterozygous variants in RP1L1.METHODS:Comprehensive retinal morphological and functional examinations were evaluated for the patient with RP1L1 maculopathy.Targeted sequence capture array technique was used to screen potential pathologic variants.Polymerase chain reaction and Sanger sequencing were used to confirm the screening results.RESULTS:Fundus examination showed round macular lesions appeared in both eyes.Optical coherence tomography showed that the inner segment/outer segment continuity was disorganized and disruptive in the left eye,but it was uneven and slightly elevated in the right eye.Fundus autofluorescence showed patchy hyper-autofluorescence in the macula.Visual field examination indicates central defects in both eyes.Electroretinogram(ERG)and multifocal ERG showed no obvious abnormalities.Fundus fluorescein angiography in the macula showed obviously irregular hyper-fluorescence in the right eye and slightly hyper-fluorescence in the left eye.We found that the proband carried a missense variant(c.1972C>T)and a deletion variant(c.4717_4718del)of RP1L1,which were originated from the parents and formed compound heterozygous variants.Both variants are likely pathogenic according to the ACMG criteria.Multimodal imaging,ERG and detailed medical history are important diagnostic tools for differentiating between acquired and inherited retinal disorders.CONCLUSION:A maculopathy case with detailed retinal phenotype and new recessive compound heterozygous variants of RP1L1 is identified in a Chinese family,which expands the understanding of phenotype and genotype in RP1L1 maculopathy.
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.
基金supported by the Natural Science Foundation of China(No.82300492)the Scientific Research Project of Health Commission in Shanxi Province,China(Nos.2023XG009 and 2023RC008)+2 种基金the China Postdoctoral Science Foundation(No.2023M732154)the Research Project Supported by Shanxi Scholarship Council of China(No.2023-181)the Fund Program for the Scientific Activities of Selected Returned Overseas Professionals in Shanxi Province,China(No.20230054).
文摘Protein C(PC)is an important physiological anticoagulant protein that is a vitamin K-dependent serine protease precursor that is synthesized mainly by the liver and released into the blood.It is activated by the thrombin/thrombomodulin complex to form activated protein C(APC),which exerts physiological anticoagulant functions by inactivating activated coagulation factors Ⅴ and Ⅷ.1 PC is encoded by the protein C gene(PROC),which is located in the q13-q14 region of chromosome 2 and consists of 9 exons and 8 introns and is approximately 11.2 kb in length.2 Individuals carrying the PROC gene variant have a risk of developing venous thrombosis that is approximately 7 times greater than that of normal individuals.PC deficiency caused by homozygous or compound heterozygous variations in the PROC gene is extremely rare.3 The prevalence rate of protein C deficiency among healthy people in China is approximately 0.29%.4 Here,we report a teenage patient with multiple recurrent deep venous thromboses associated with protein C deficiency caused by compound heterozygous variants that have not been previously reported.
基金supported by the National Natural Science Foundation of China(No.82272446).
文摘Titin,the largest known protein in nature,is a giant sarcomeric protein that plays essential architectural,developmental,and regulatory roles in striated muscles.Mutations in the TTN gene(MIM:188840)that encodes titin are related to a broad range of muscle diseases known as titinopathies,with diverse clinical manifestations including weakness,contractures,scoliosis,respiratory failure,and cardiomyopathy.1 In this case report,we describe two sisters with severe scoliosis,both carrying novel compound heterozygous variants in the TTN gene,yet presenting distinct clinical phenotypes,adding to the growing body of evidence linking TTN mutations to scoliosis and other titinrelated disorders.
文摘Objective:Glucose-6-phosphate isomerase(GPI)deficiency is a rare hereditary nonspherocytic hemolytic anemia caused by GPI gene variants.This disorder exhibits wide heterogeneity in its clinical manifestations and molecular characteristics,often posing challenges for precise diagnoses using conventional methods.To this end,this study aimed to identify the novel variants responsible for GPI deficiency in a Chinese family.Methods:The clinical manifestations of the patient were summarized and analyzed for GPI deficiency phenotype diagnosis.Novel compound heterozygous variants of the GPI gene,c.174C>A(p.Asn58Lys)and c.1538G>T(p.Trp513Leu),were identified using whole-exome and Sanger sequencing.The AlphaFold program and Chimera software were used to analyze the effects of compound heterozygous variants on GPI structure.Results:By characterizing 53 GPI missense/nonsense variants from previous literature and two novel missense variants identified in this study,we found that most variants were located in exons 3,4,12,and 18,with a few localized in exons 8,9,and 14.This study identified novel compound heterozygous variants associated with GPI deficiency.These pathogenic variants disrupt hydrogen bonds formed by highly conserved GPI amino acids.Conclusion:Early family-based sequencing analyses,especially for patients with congenital anemia,can help increase diagnostic accuracy for GPI deficiency,improve child healthcare,and enable genetic counseling.
文摘Objective To analyze the clinical phenotypes and genetic features of a child with developmental and epileptic encephalopathy due to compound heterozygous variants in the ALG14 gene,and to improve clinicians'understanding of the ALG14 gene and its associated disorders.
