National Fragile X Foundation, Walnut Creek, CA 94596, USA.
Pediatrics. 2012 Dec;130(6):1126-35. doi: 10.1542/peds.2012-0693. Epub 2012 Nov 5.
Fragile X syndrome, diagnosed by Fragile X Mental Retardation 1 (FMR1) DNA testing, is the most common single-gene cause of inherited intellectual disability. The expanded CGG mutation in the FMR1 gene, once thought to have clinical significance limited to fragile X syndrome, is now well established as the cause for other fragile X-associated disorders including fragile X-associated primary ovarian insufficiency and fragile X-associated tremor ataxia syndrome in individuals with the premutation (carriers). The importance of early diagnostic and management issues, in conjunction with the identification of family members at risk for or affected by FMR1 mutations, has led to intense discussion about the appropriate timing for early identification of FMR1 mutations. This review includes an overview of the fragile X-associated disorders and screening efforts to date, and discussion of the advantages and barriers to FMR1 screening in newborns, during childhood, and in women of reproductive age. Comparison with screening programs for other common genetic conditions is discussed to arrive at action steps to increase the identification of families affected by FMR1 mutations.
脆性 X 综合征是最常见的单基因遗传性智力障碍，通过脆性 X 智力低下 1 号基因（FMR1）DNA 检测即可诊断。FMR1 基因中 CGG 重复扩增突变曾被认为仅与脆性 X 综合征有关，但现在已明确其为脆性 X 相关疾病的病因之一，包括脆性 X 相关原发性卵巢功能不全和脆性 X 相关震颤共济失调综合征，这些疾病发生在具有前突变（携带者）的个体中。早期诊断和管理问题的重要性，以及识别脆性 X 突变风险或受影响的家族成员，促使人们对早期识别 FMR1 突变的适当时机进行了激烈的讨论。这篇综述包括对脆性 X 相关疾病和迄今为止的筛查工作的概述，以及对新生儿期、儿童期和生育年龄妇女进行 FMR1 筛查的优势和障碍的讨论。与其他常见遗传疾病的筛查计划进行比较，以确定增加受 FMR1 突变影响的家庭识别的步骤。
