MOLECULAR ANALYSIS OF NEW MUTATIONS FOR HUNTINGTONS-DISEASE - INTERMEDIATE ALLELES AND SEX OF ORIGIN EFFECTS
MOLECULAR ANALYSIS OF NEW MUTATIONS FOR HUNTINGTONS-DISEASE - INTERMEDIATE ALLELES AND SEX OF ORIGIN EFFECTS
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DOI：
10.1038/ng1093-174
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发表时间：
1993-10-01
期刊：
影响因子：
30.8
通讯作者：
HAYDEN, MR
中科院分区：
文献类型：
--
作者：
GOLDBERG, YP;KREMER, B;HAYDEN, MR
亨廷顿病(HD)与一种新基因中CAG重复序列的扩大有关。我们评估了21个散发性HD病例，以调查HD背后的顺序事件。我们发现在HD基因中30-38个CAG重复的亲本等位基因中存在一个中间等位基因(IA)，这比通常在普通人群中看到的要大，但低于HD患者的范围。这些IAS在减数分裂中是不稳定的，在零星病例中，扩展到与HD表型相关的全部突变。这种扩张被证明只发生在通过男性生殖系传播的过程中，并与父亲的高龄有关。这些发现表明，HD的新突变比先前估计的更频繁，并表明散发性HD的兄弟姐妹及其子女存在先前未被认识到的遗传HD的风险。
Huntington's disease (HD) is associated with expansion of a CAG repeat in a novel gene. We have assessed 21 sporadic cases of HD to investigate sequential events underlying HD. We show the existence of an intermediate allele (IA) in parental alleles of 30-38 CAG repeats in the HD gene which is greater than usually seen in the general population but below the range seen in patients with HD. These IAs are meiotically unstable and in the sporadic cases, expand to the full mutation associated with the phenotype of HD. This expansion has been shown to occur only during transmission through the male germline and is associated with advanced paternal age. These findings suggest that new mutations for HD are more frequent than prior estimates and indicate a previously unrecognized risk of inheriting HD to siblings of sporadic cases of HD and their children.