No Evidence for a Difference in Neuropsychological Profile among Carriers and Noncarriers of the FMR1 Premutation in Adults under the Age of 50
No Evidence for a Difference in Neuropsychological Profile among Carriers and Noncarriers of the FMR1 Premutation in Adults under the Age of 50
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DOI：
10.1016/j.ajhg.2008.10.021
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发表时间：
2008-12-12
影响因子：
9.8
通讯作者：
Sherman, Stephanie L.
中科院分区：
文献类型：
--
作者：
Hunter, Jessica Ezzell;Allen, Emily Graves;Sherman, Stephanie L.
脆性 X 智力低下基因 FMR1 的 5' 非翻译区包含多态性 CGG 重复序列。这种重复的扩展与一系列疾病有关。完全突变等位基因（重复次数 >= 200）与脆性 X 综合征相关。前突变等位基因（重复次数类似于 55-199）与老年男性中最常见的震颤共济失调综合征和女性中的原发性卵巢功能不全有关。然而，携带前突变等位基因对年轻人的神经心理学影响目前尚不清楚。在这项研究中，我们分析了 138 名男性和 506 名女性的神经心理学评分，这些评分来自普通人群和有脆性 X 综合征病史的家庭。受试者年龄为 18-50 岁，重复长度各不相同。神经心理学评分是通过一般智力、记忆力和执行功能（包括注意力）的测量获得的。使用主成分分析和最大方差旋转来创建用于分析的独立因素。这些因素通过考虑相关受试者之间相关性的一般线性模型分别为男性和女性建模。所有模型都针对潜在的混杂因素进行了调整，包括测试年龄、种族和家庭收入。在男性中，没有检测到任何因素的重复长度关联。在女性中，仅检测到重复长度和自我报告注意力之间存在显着相关性（p < 0.01），与非携带者相比，前突变携带者自我报告的注意力相关问题明显更多。没有检测到重复长度和年龄之间存在显着的相互作用。总体而言，这些结果表明携带前突变等位基因对 50 岁以下成年人缺乏整体神经心理学影响。
The 5' untranslated region of the fragile X mental retardation gene, FMR1, contains a polymorphic CGG repeat. Expansions of this repeat are associated with a spectrum of disorders. Full mutation alleles, repeats >= 200, are associated with fragile X syndrome. Premutation alleles, repeats of similar to 55-199, are associated with a tremor-ataxia syndrome most commonly in older males and primary ovarian insufficiency in females. However, the neuropsychological impact of carrying a premutation allele is presently unclear in younger adults. In this study, we analyzed neuropsychological scores for 138 males and 506 females ascertained from the general population and from families with a history of fragile X syndrome. Subjects were age 18-50 years and had varying repeat lengths. Neuropsychological scores were obtained from measures of general intelligence, memory, and executive functioning, including attention. Principal component analysis followed by varimax rotation was used to create independent factors for analysis. These factors were modeled for males and females separately via a general linear model that accounted for correlation among related subjects. All models were adjusted for potential confounders, including age at testing, ethnicity, and household income. Among males, no repeat length associations were detected for any factor. Among females, only a significant association with repeat length and self-report attention (p < 0.01) was detected, with premutation carriers self-reporting significantly more attention-related problems compared to noncarriers. No significant interactions between repeat length and age were detected. Overall, these results indicate the lack of a global neuropsychological impact of carrying a premutation allele among adults under the age of 50.