We report a young girl with a phenotype combining early-on-set myopathy a nd a progeria. She had myopathy and marked axial weakness during the first year of life; progeroid features, including growth failure, sclerode...We report a young girl with a phenotype combining early-on-set myopathy a nd a progeria. She had myopathy and marked axial weakness during the first year of life; progeroid features, including growth failure, sclerodermatous skin chan ges, and osteolytic lesions, developed later. We identified the underlying cause to be a hitherto unreported de novo missense mutation in the LMNA gene (S143F) encoding the nuclear envelope proteins lamins A and C. Although LMNA mutations h ave been known to cause Hutchinson-Gilford progeria syndrome and Emery-Dreif uss muscular dystrophy, this is the first report of a patient combining features of these two phenotypes because of a single mutation in LMNA.展开更多
Background:Werner syndrome (WS) is a rare autosomal recessive progeroid disorder caused by mutations of the WRN gene encoding a protein of the RecQ-type family of DNA helicases. Objectives:To develop a rapid and simpl...Background:Werner syndrome (WS) is a rare autosomal recessive progeroid disorder caused by mutations of the WRN gene encoding a protein of the RecQ-type family of DNA helicases. Objectives:To develop a rapid and simple reverse transcription-polymerase chain reaction (RT-PCR) strategy for mutation analysis of the WRN gene, to identify pathogenic mutations in a German patient with WS and to determine the effects of the pathogenic mutations on WRN mRNA stability. Methods:Allele-specific RT-PCR, semiquantitative RT-PCR, DNA sequencing. Results:We describe a novel and rapid RT-PCR-based method for mutation analysis in WS and report a German patient with WS carrying a previously reported (1396delA) as well as a novel nonsense mutation (2334delAC)of the WRN gene. By semiquantitative RT-PCR analysis we demonstrate that this compound heterozygous genotype leads to WRN transcript decay. Conclusions:In previous studies WS was primarily attributed to a loss of function of stable truncated WRN gene products. Our findings indicate that mutations can also lead to markedly decreased WRN transcript stability.展开更多
文摘Hutch inson-G ilford早老症(HGPS)为一种极为罕见的遗传性疾病,发生率1/8000000,特征性表现为患儿以极快速度衰老,多数死于冠脉病变引起的心肌梗死或广泛动脉粥样硬化导致的卒中,平均寿命13岁。绝大多数HGPS病例病因为LMNA基因第11个外显子发生点突变(G608G),生成的突变lam in A由显性负效应造成细胞核结构和功能受损。目前该病已有几种动物模型,实验性治疗可以在体外将出泡的细胞核恢复正常。HGPS是研究衰老和心血管疾病机制的一个极好的模型。
文摘We report a young girl with a phenotype combining early-on-set myopathy a nd a progeria. She had myopathy and marked axial weakness during the first year of life; progeroid features, including growth failure, sclerodermatous skin chan ges, and osteolytic lesions, developed later. We identified the underlying cause to be a hitherto unreported de novo missense mutation in the LMNA gene (S143F) encoding the nuclear envelope proteins lamins A and C. Although LMNA mutations h ave been known to cause Hutchinson-Gilford progeria syndrome and Emery-Dreif uss muscular dystrophy, this is the first report of a patient combining features of these two phenotypes because of a single mutation in LMNA.
文摘Background:Werner syndrome (WS) is a rare autosomal recessive progeroid disorder caused by mutations of the WRN gene encoding a protein of the RecQ-type family of DNA helicases. Objectives:To develop a rapid and simple reverse transcription-polymerase chain reaction (RT-PCR) strategy for mutation analysis of the WRN gene, to identify pathogenic mutations in a German patient with WS and to determine the effects of the pathogenic mutations on WRN mRNA stability. Methods:Allele-specific RT-PCR, semiquantitative RT-PCR, DNA sequencing. Results:We describe a novel and rapid RT-PCR-based method for mutation analysis in WS and report a German patient with WS carrying a previously reported (1396delA) as well as a novel nonsense mutation (2334delAC)of the WRN gene. By semiquantitative RT-PCR analysis we demonstrate that this compound heterozygous genotype leads to WRN transcript decay. Conclusions:In previous studies WS was primarily attributed to a loss of function of stable truncated WRN gene products. Our findings indicate that mutations can also lead to markedly decreased WRN transcript stability.
