ANDROGEN RECEPTOR GENE-MUTATIONS IN X-LINKED SPINAL AND BULBAR MUSCULAR-ATROPHY
ANDROGEN RECEPTOR GENE-MUTATIONS IN X-LINKED SPINAL AND BULBAR MUSCULAR-ATROPHY
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DOI：
10.1038/352077a0
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发表时间：
1991-07-04
期刊：
影响因子：
64.8
通讯作者：
FISCHBECK, KH
中科院分区：
文献类型：
--
作者：
LASPADA, AR;WILSON, EM;FISCHBECK, KH
X-连锁脊髓延髓肌萎缩症（肯尼迪病）是一种成年发病形式的运动神经元疾病，可能与雄激素不敏感的体征有关。我们现在已经研究了X染色体近端长臂上的雄激素受体基因是否是这种疾病的候选基因。在患者样本中，我们发现雄激素受体基因突变，编码区多态性串联CAG重复序列大小增加。这些扩增的重复序列与疾病绝对相关，存在于35名无关患者中，而75名对照中没有。它们在15个家系中与疾病分离，在61个减数分裂中没有重组（重组率为0时的最大对数似然比（lod得分）为13.2）。这种关联不太可能是由于连锁不平衡，因为观察到11种不同的疾病等位基因。我们的结论是雄激素受体基因CAG重复的扩大可能是这种疾病的原因。
X-LINKED spinal and bulbar muscular atrophy (Kennedy's disease) is an adult-onset form of motorneuron disease which may be associated with signs of androgen insensitivity. We have now investigated whether the androgen receptor gene on the proximal long arm of the X chromosome is a candidate gene for this disease. In patient samples we found androgen receptor gene mutations with increased size of a polymorphic tandem CAG repeat in the coding region. These amplified repeats were absolutely associated with the disease, being present in 35 unrelated patients and none of 75 controls. They segregated with the disease in 15 families, with no recombination in 61 meioses (the maximum log likelihood ratio (lod score) is 13.2 at a recombination rate of 0). The association is unlikely to be due to linkage disequilibrium, because 11 different disease alleles were observed. We conclude that enlargement of the CAG repeat in the androgen receptor gene is probably the cause of this disorder.