由错义突变引起的脆性X综合征。
Fragile X syndrome due to a missense mutation.
作者信息
Myrick Leila K, Nakamoto-Kinoshita Mika, Lindor Noralane M, Kirmani Salman, Cheng Xiaodong, Warren Stephen T
机构信息
Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
Department of Health Science Research, Mayo Clinic, Scottsdale, AZ, USA.
出版信息
Eur J Hum Genet. 2014 Oct;22(10):1185-9. doi: 10.1038/ejhg.2013.311. Epub 2014 Jan 22.
Abstract
Fragile X syndrome is a common inherited form of intellectual disability and autism spectrum disorder. Most patients exhibit a massive CGG-repeat expansion mutation in the FMR1 gene that silences the locus. In over two decades since the discovery of FMR1, only a single missense mutation (p.(Ile304Asn)) has been reported as causing fragile X syndrome. Here we describe a 16-year-old male presenting with fragile X syndrome but without the repeat expansion mutation. Rather, we find a missense mutation, c.797G>A, that replaces glycine 266 with glutamic acid (p.(Gly266Glu)). The Gly266Glu FMR protein abolished many functional properties of the protein. This patient highlights the diagnostic utility of FMR1 sequencing.
摘要
脆性X综合征是一种常见的遗传性智力残疾和自闭症谱系障碍。大多数患者在FMR1基因中表现出大量CGG重复扩增突变，该突变使该基因座沉默。自发现FMR1基因以来的二十多年里，仅报道了一个错义突变（p.(Ile304Asn)）可导致脆性X综合征。在此，我们描述了一名16岁男性，患有脆性X综合征，但无重复扩增突变。相反，我们发现了一个错义突变c.797G>A，该突变将甘氨酸266替换为谷氨酸（p.(Gly266Glu)）。Gly266Glu FMR蛋白消除了该蛋白的许多功能特性。该患者突出了FMR1基因测序的诊断效用。
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