男性脆性X综合征患者FMR - 1基因的完全突变在其精子中不存在。

The full mutation in the FMR-1 gene of male fragile X patients is absent in their sperm.

作者信息

Reyniers E, Vits L, De Boulle K, Van Roy B, Van Velzen D, de Graaff E, Verkerk A J, Jorens H Z, Darby J K, Oostra B

机构信息

Department of Medical Genetics, University of Antwerp-ULA, Belgium.

出版信息

Nat Genet. 1993 Jun;4(2):143-6. doi: 10.1038/ng0693-143.

DOI:10.1038/ng0693-143

PMID:8348152

Abstract

Fragile X syndrome is characterized at the molecular level by amplification of a (CGG)n repeat and hypermethylation of a CpG island preceeding the open reading frame of the fragile X gene (FMR-1) located in Xq27.3. Anticipation in this syndrome is associated with progressive amplification of the (CGG)n repeat from a premutation to a full mutation through consecutive generations. Remarkably, expansion of the premutation to the full mutation is strictly maternal. To clarify this parental influence we studied FMR-1 in sperm of four male fragile X patients. This showed that only the premutation was present in their sperm, although they had a full mutation in peripheral lymphocytes. This might suggest that expansion of the premutation to the full mutation in FMR-1 does not occur in meiosis but in a postzygotic stage.

摘要

脆性X综合征在分子水平上的特征是位于Xq27.3的脆性X基因（FMR-1）开放阅读框之前的（CGG）n重复序列扩增以及CpG岛的高甲基化。该综合征中的遗传早现与（CGG）n重复序列通过连续几代从前突变逐步扩增为全突变有关。值得注意的是，前突变扩展为全突变严格为母系遗传。为了阐明这种亲代影响，我们研究了四名男性脆性X患者精子中的FMR-1。结果显示，尽管他们外周淋巴细胞中存在全突变，但精子中仅存在前突变。这可能表明FMR-1中前突变扩展为全突变并非发生在减数分裂过程中，而是发生在合子后阶段。