More than 40 CGG expansions in the 5' noncoding region of the fragile X mental retardation 1(FMR1)gene of the X chromosome give rise to several distinct clinical phenotypes, depending on the size of the expansion....More than 40 CGG expansions in the 5' noncoding region of the fragile X mental retardation 1(FMR1)gene of the X chromosome give rise to several distinct clinical phenotypes, depending on the size of the expansion. First, more than 200 CGG expansions(full mutation) cause an inherited mental retardation called fragile X syndrome. Second, CGG expansions between55 and 199(premutation) cause a disorder called fragile X-associated tremor/ataxia syndrome(FXTAS) which typically includes intention tremor, ataxia and specific magnetic resonance imaging(MRI) findings. Indeed, it could develop parkinsonism although it usually shows features of postsynaptic parkinsonism. Finally, CGG expansions between 41 and 54 CGG(gray zone) are not consider normal but rarely develops abnormal neurological conditions. In this sense, the aim of this study is to report two atypical cases associated with CGG expansions of the FMR1 gene. First, a FMR1 premutation alleles carrier with an unusual phenotype, such as a presynaptic parkinsonism indistinguishable from Parkinson disease(PD) and a FMR1 gray zone alleles carrier presented with neurological features, namely hand tremor, parkinsonism and ataxia, usually described in FXTAS, as well as orthostatic tremor. We conclude that,on the one hand, FMR1 premutation alleles might cause two phenotypes of parkinsonism, such as a presynaptic phenotype, indistinguishable from PD, and a postsynaptic phenotype, associated with clinical features of FXTAS. On the other hand, although FMR1 gray zone alleles carriers were believed to have no abnormal neurological conditions, our study supports that they could develop FXTAS and other neurological disorders such as orthostatic tremor which has not been reported before associated with the FMR1 gene.展开更多
脆性X相关性疾病(FragileXassociatedDisorders,FXD)是由脆性X智力低下蛋白(FragileXMental Retardation Protein,FMRP)部分或完全丧失引起的家族遗传性疾病。其中脆性X综合征(Fragile X syndrome,FXS)是遗传性智力残疾和自闭症的最常...脆性X相关性疾病(FragileXassociatedDisorders,FXD)是由脆性X智力低下蛋白(FragileXMental Retardation Protein,FMRP)部分或完全丧失引起的家族遗传性疾病。其中脆性X综合征(Fragile X syndrome,FXS)是遗传性智力残疾和自闭症的最常见原因之一,其发病率仅次于唐氏综合征,占非特发性智力低下患者的2%-6%,在X连锁智力低下患者中占40%。FXD临床表现不典型,遗传方式多样化。本文将从FXD的临床表现,FMR1基因及其致病机制,FMRP结构及其对转录翻译过程中的影响等方面进行综述。展开更多
文摘More than 40 CGG expansions in the 5' noncoding region of the fragile X mental retardation 1(FMR1)gene of the X chromosome give rise to several distinct clinical phenotypes, depending on the size of the expansion. First, more than 200 CGG expansions(full mutation) cause an inherited mental retardation called fragile X syndrome. Second, CGG expansions between55 and 199(premutation) cause a disorder called fragile X-associated tremor/ataxia syndrome(FXTAS) which typically includes intention tremor, ataxia and specific magnetic resonance imaging(MRI) findings. Indeed, it could develop parkinsonism although it usually shows features of postsynaptic parkinsonism. Finally, CGG expansions between 41 and 54 CGG(gray zone) are not consider normal but rarely develops abnormal neurological conditions. In this sense, the aim of this study is to report two atypical cases associated with CGG expansions of the FMR1 gene. First, a FMR1 premutation alleles carrier with an unusual phenotype, such as a presynaptic parkinsonism indistinguishable from Parkinson disease(PD) and a FMR1 gray zone alleles carrier presented with neurological features, namely hand tremor, parkinsonism and ataxia, usually described in FXTAS, as well as orthostatic tremor. We conclude that,on the one hand, FMR1 premutation alleles might cause two phenotypes of parkinsonism, such as a presynaptic phenotype, indistinguishable from PD, and a postsynaptic phenotype, associated with clinical features of FXTAS. On the other hand, although FMR1 gray zone alleles carriers were believed to have no abnormal neurological conditions, our study supports that they could develop FXTAS and other neurological disorders such as orthostatic tremor which has not been reported before associated with the FMR1 gene.
文摘脆性X相关性疾病(FragileXassociatedDisorders,FXD)是由脆性X智力低下蛋白(FragileXMental Retardation Protein,FMRP)部分或完全丧失引起的家族遗传性疾病。其中脆性X综合征(Fragile X syndrome,FXS)是遗传性智力残疾和自闭症的最常见原因之一,其发病率仅次于唐氏综合征,占非特发性智力低下患者的2%-6%,在X连锁智力低下患者中占40%。FXD临床表现不典型,遗传方式多样化。本文将从FXD的临床表现,FMR1基因及其致病机制,FMRP结构及其对转录翻译过程中的影响等方面进行综述。
