Penetrance of the fragile X - Associated tremor/ataxia syndrome in a premutation carrier population
Penetrance of the fragile X - Associated tremor/ataxia syndrome in a premutation carrier population
复制标题
DOI：
10.1001/jama.291.4.460
复制
发表时间：
2004-01-28
影响因子：
120.7
通讯作者：
Hagerman, PJ
中科院分区：
文献类型：
--
作者：
Jacquemont, S;Hagerman, RJ;Hagerman, PJ
脆性X智力低下1（FMR 1）基因的前突变扩增（55-200 CGG重复）在一般人群中很常见，估计患病率为每259名女性和每813名男性中有1人。最近有几篇文章描述了前突变（FMR 1）等位基因男性携带者迟发性神经系统症状的存在。这种新发现的综合征的主要临床特征是小脑共济失调和意向性震颤。其他记录的症状包括短期记忆丧失、执行功能缺陷、认知能力下降、帕金森综合征、周围神经病变、下肢近端肌无力和自主神经功能障碍。目的研究脆性X相关震颤/共济失调综合征（FXTAS）在前突变携带者中的发病率。和参与者192个个体（前突变携带者和对照）的家庭为基础的研究属于北方或南方加州脆性X染色体协会。收集数据（2002年3月至2003年4月）通过调查和标准化神经系统检查，主要指标成人携带者意向性震颤和共济失调的外显率（年龄大于或等于50岁）的FMR 1基因的前突变扩增。在男性携带者中，所报告的意向性震颤和步态共济失调组合的相关发病率（50-59岁、60-69岁、70-79岁和大于或等于80岁的参与者分别为17%、38%、47%和75% [下限估计值]）。与男性对照组相比，男性携带者组合并意向性震颤和步态共济失调的年龄调整风险增加13倍（95%置信区间，3.9-25.4; P= 0.003）。93例临床检查资料显示，男性携带者在3个标准化神经功能评定量表上均较对照组困难（P
Context Premutation expansions (55-200 CGG repeats) of the fragile X mental retardation 1 (FMR1) gene are frequent in the general population, with estimated prevalences of 1 per 259 females and 1 per 813 males. Several articles have recently described the presence of late-onset neurological symptoms in male carriers of premutation (FMR1) alleles. The main clinical features described in this newly identified syndrome are cerebellar ataxia and intention tremor. Additional documented symptoms include short-term memory loss, executive functional deficits, cognitive decline, parkinsonism, peripheral neuropathy, lower-limb proximal muscle weakness, and autonomic dysfunction.Objective To study the penetrance of the fragile X-associated tremor/ataxia syndrome (FXTAS) among premutation carriers.Design, Setting, and Participants Family-based study of 192 individuals (premutation carriers and controls) whose families belong to the Northern or Southern California Fragile X Associations. Data were collected (March 2002-April 2003) through a survey and a standardized neurological examination, which was videotaped and subsequently scored in a blinded fashion.Main Outcome Measures Penetrance of intention tremor and ataxia among adult carriers (aged greater than or equal to50 years) of premutation expansions of the FMR1 gene.Results Data from the survey of 192 individuals demonstrated an age-related penetrance of the combination of reported intention tremor and gait ataxia in male carriers (17%, 38%, 47%, and 75% [lower-bound estimates] for participants aged 50-59, 60-69, 70-79, and greater than or equal to80 years, respectively). The male carrier group had an age-adjusted 13-fold increased risk (95% confidence interval, 3.9-25.4; P=.003) of combined intention tremor and gait ataxia when compared with male controls. The clinical examination data from 93 individuals demonstrated that male carriers experienced more difficulties on each of 3 standardized neurological rating scales compared with controls (P