A disorder similar to Huntington's disease is associated with a novel CAG repeat expansion
A disorder similar to Huntington's disease is associated with a novel CAG repeat expansion
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DOI：
10.1002/ana.1312
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发表时间：
2001-09-01
影响因子：
11.2
通讯作者：
Ross, CA
中科院分区：
文献类型：
--
作者：
Margolis, RL;O'Hearn, E;Ross, CA
亨廷顿病(HD)是一种常染色体显性遗传性疾病，以运动、认知、情绪异常和选择性纹状体萎缩为特征。和大脑皮层。虽然已知HD的病因是CAG三核苷酸重复扩增，但这种突变导致HD病理的途径仍不清楚。我们现在报告一个常染色体显性遗传病的大型家系，临床上类似于HD，由不同的CAG扩展突变引起。这种疾病的特点是在第四个十年起病，不自主运动和自主运动异常，精神症状，体重减轻，痴呆症，以及在发病后约20年死亡的无情过程。脑磁共振成像扫描和尸检显示明显的纹状体萎缩和中度的皮质萎缩，纹状体神经变性位于背侧到腹侧的梯度，偶尔有核内包涵体。根据重复扩增检测分析，所有检测的受影响个体，以及没有检测的未受影响的个体，CAG三核苷酸重复扩增50至60个三联体。HD扩增、所有其他已知的CAG扩增突变以及与染色体20p和4p的连锁检测均为阴性，表明该突变是新的。克隆这种新疾病的致病CAG扩增突变，我们称之为亨廷顿病样2，可能为HD和相关疾病的发病机制提供有价值的见解。
Huntington's disease (HD) is an autosomal dominant disorder characterized by abnormalities of movement, cognition, and emotion and selective atrophy of the striatum. and cerebral cortex. While the etiology of HD is known to be a CAG trinucleotide repeat expansion, the pathways by which this mutation causes HD pathology remain unclear. We now report a large pedigree with an autosomal dominant disorder that is clinically similar to HD and that arises from a different CAG expansion mutation. The disorder is characterized by onset in the fourth decade, involuntary movements and abnormalities of voluntary movement, psychiatric symptoms, weight loss, dementia, and a relentless course with death about 20 years after disease onset. Brain magnetic resonance imaging scans and an autopsy revealed marked striatal atrophy and moderate cortical atrophy, with striatal neurodegeneration in a dorsal to ventral gradient and occasional intranuclear inclusions. All tested affected individuals, and no tested unaffecteds, have a CAG trinucleotide repeat expansion of 50 to 60 triplets, as determined by the repeat expansion detection assay. Tests for the HD expansion, for all other known CAG expansion mutations, and for linkage to chromosomes 20p and 4p were negative, indicating that this mutation is novel. Cloning the causative CAG expansion mutation for this new disease, which we have termed Huntington's disease-like 2, may yield valuable insight into the pathogenesis of HD and related disorders.