Background： SH3TC2, PMP2, and BSCL2 genes are related to autosomal recessive （AR） Charcot-Marie-Tooth （CMT） disease type 1, autosomal dominant （AD）-CMTI, and AD-CMT2, respectively. Pathogenic variants in these ...Background： SH3TC2, PMP2, and BSCL2 genes are related to autosomal recessive （AR） Charcot-Marie-Tooth （CMT） disease type 1, autosomal dominant （AD）-CMTI, and AD-CMT2, respectively. Pathogenic variants in these three genes were not well documented in Chinese CMT patients. Therefore, this study aims to detect SH3TC2, PMP2, and BSCL2 pathogenic variants in a cohort of 315 unrelated Chinese CMT families. Methods： A total of 315 probands from 315 unrelated Chinese CMT families were recruited from the Department of Neurology of Third Xiangya Hospital and Xiangya Hospital. We screened for SH3TC2 pathogenic variants in 84 AR or sporadic CMT probands, PMP2 pathogenic variants in 39 AD or sporadic CMTI probands, and BSCL2 pathogenic variants in 50 AD or sporadic CMT2 probands, using polymerase chain reaction and Sanger sequencing. All these patients were out of 315 unrelated Chinese CMT families and genetically undiagnosed after exclusion of pathogenic variants of PMP22, MFN2, MPZ, GJB 1, GDAP1, HSPB1, HSPB8, EGR2, NEFL. and RABT. Candidate variants were analyzed based on the standards and guidelines of American College of Medical Genetics and Genomics （ACMG）. Clinical features were reevaluated. Results： We identified three novel heterozygous variants such as p.L95V （c.283C〉G）, p.L 1048P （c.3143T〉C）, and p.V 1105 M （c.3313G〉A） of SH3TC2 gene and no pathogenic variants of PMP2 and BSCL2 genes. Although evaluation in silico and screening in the healthy control revealed that the three SH3TC2 variants were likely pathogenic, no second allele variants were discovered. According to the standards and guidelines of ACMG, the heterozygous SH3TC2 variants such as p.L95V, p.LI048P, and p.V1105M were considered to be of uncertain significance. Conclusions： SH3TC2, PMP2, and BSCL2 pathogenic variants might be rare in Chinese CMT patients. Further studies to confirm our findings are needed.展开更多
Transthyretin-related familial amyloid polyneuropathy(TTR-FAP)is an autosomal dominant,life-threatening,and treatable disorder caused by TTR mutation.It is characterized by amyloid deposition in the peripheral nerves ...Transthyretin-related familial amyloid polyneuropathy(TTR-FAP)is an autosomal dominant,life-threatening,and treatable disorder caused by TTR mutation.It is characterized by amyloid deposition in the peripheral nerves and major organs,including the heart,kidneys,and eyes.So far,more than 130 TTR mutations have been identified,in which p.Val30Met is the most common in endemic countries.TTR-FAP has been reported in 29 countries,including many countries in Europe,USA,Japan,China,and India.Clinical and genetic features of TTR-FAP are relatively clear in Europe and Japan,however,it still need to be carried out in China.Here,we reported the clinical and genetic features of 8 Chinese TTR-FAP families.展开更多
文摘Background： SH3TC2, PMP2, and BSCL2 genes are related to autosomal recessive （AR） Charcot-Marie-Tooth （CMT） disease type 1, autosomal dominant （AD）-CMTI, and AD-CMT2, respectively. Pathogenic variants in these three genes were not well documented in Chinese CMT patients. Therefore, this study aims to detect SH3TC2, PMP2, and BSCL2 pathogenic variants in a cohort of 315 unrelated Chinese CMT families. Methods： A total of 315 probands from 315 unrelated Chinese CMT families were recruited from the Department of Neurology of Third Xiangya Hospital and Xiangya Hospital. We screened for SH3TC2 pathogenic variants in 84 AR or sporadic CMT probands, PMP2 pathogenic variants in 39 AD or sporadic CMTI probands, and BSCL2 pathogenic variants in 50 AD or sporadic CMT2 probands, using polymerase chain reaction and Sanger sequencing. All these patients were out of 315 unrelated Chinese CMT families and genetically undiagnosed after exclusion of pathogenic variants of PMP22, MFN2, MPZ, GJB 1, GDAP1, HSPB1, HSPB8, EGR2, NEFL. and RABT. Candidate variants were analyzed based on the standards and guidelines of American College of Medical Genetics and Genomics （ACMG）. Clinical features were reevaluated. Results： We identified three novel heterozygous variants such as p.L95V （c.283C〉G）, p.L 1048P （c.3143T〉C）, and p.V 1105 M （c.3313G〉A） of SH3TC2 gene and no pathogenic variants of PMP2 and BSCL2 genes. Although evaluation in silico and screening in the healthy control revealed that the three SH3TC2 variants were likely pathogenic, no second allele variants were discovered. According to the standards and guidelines of ACMG, the heterozygous SH3TC2 variants such as p.L95V, p.LI048P, and p.V1105M were considered to be of uncertain significance. Conclusions： SH3TC2, PMP2, and BSCL2 pathogenic variants might be rare in Chinese CMT patients. Further studies to confirm our findings are needed.
基金grants from the National Natural Science Foundation of China(No.81771366)the Hunan Provincial Natural Science Foundation of China(No.2017JJ2365)+1 种基金the Science Foundation of Health and Family Planning Commission of Hunan Province(No.A2017001)the National Key Plan for Scientific Research and Development of China(No.2016YFC1306000)。
文摘Transthyretin-related familial amyloid polyneuropathy(TTR-FAP)is an autosomal dominant,life-threatening,and treatable disorder caused by TTR mutation.It is characterized by amyloid deposition in the peripheral nerves and major organs,including the heart,kidneys,and eyes.So far,more than 130 TTR mutations have been identified,in which p.Val30Met is the most common in endemic countries.TTR-FAP has been reported in 29 countries,including many countries in Europe,USA,Japan,China,and India.Clinical and genetic features of TTR-FAP are relatively clear in Europe and Japan,however,it still need to be carried out in China.Here,we reported the clinical and genetic features of 8 Chinese TTR-FAP families.
