C9orf72 expansions are the most common genetic cause of Huntington disease phenocopies
C9orf72 expansions are the most common genetic cause of Huntington disease phenocopies
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DOI：
10.1212/wnl.0000000000000061
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发表时间：
2014-01-28
期刊：
影响因子：
9.9
通讯作者：
Tabrizi, Sarah J.
中科院分区：
文献类型：
--
作者：
Moss, Davina J. Hensman;Poulter, Mark;Tabrizi, Sarah J.
目的：在许多疑似亨廷顿病（HD）的病例中，HD的基因检测结果为阴性：这些被称为HD拟表型。C9orf72基因的重复扩增最近被确定为家族性和散发性额颞叶变性和肌萎缩侧索硬化症的主要原因。我们的目的是确定这种突变是否会导致HD phenocopies.Methods：一个队列的514 HD phenocopiespatients进行了分析C9orf72扩增使用重复引物PCR。在发现扩增的情况下，进行Southern杂交以确定扩增大小。临床病例笔记进行了审查，以确定扩张阳性cases.Results的表型：10名受试者（1.95%）的扩张，使其成为最常见的确定HD表型介绍的遗传原因。扩张的大小与C9orf72扩张病例的其他临床表现无显著差异。C9orf72扩增阳性受试者的特征是存在运动障碍，包括肌张力障碍、舞蹈病、肌阵挛、震颤和僵硬。此外，在这个队列中发病的年龄低于以前报道的C9orf72扩展的受试者，包括一个与儿科onset.Discussion：这项研究扩展了已知的表型C9orf72扩展在发病年龄和运动障碍症状。我们提出了一个修订后的临床遗传算法的调查HD表型患者的基础上，这些数据。
Objective:In many cases where Huntington disease (HD) is suspected, the genetic test for HD is negative: these are known as HD phenocopies. A repeat expansion in the C9orf72 gene has recently been identified as a major cause of familial and sporadic frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Our objective was to determine whether this mutation causes HD phenocopies.Methods:A cohort of 514 HD phenocopy patients were analyzed for the C9orf72 expansion using repeat primed PCR. In cases where the expansion was found, Southern hybridization was performed to determine expansion size. Clinical case notes were reviewed to determine the phenotype of expansion-positive cases.Results:Ten subjects (1.95%) had the expansion, making it the most common identified genetic cause of HD phenocopy presentations. The size of expansion was not significantly different from that associated with other clinical presentations of C9orf72 expanded cases. The C9orf72 expansion-positive subjects were characterized by the presence of movement disorders, including dystonia, chorea, myoclonus, tremor, and rigidity. Furthermore, the age at onset in this cohort was lower than previously reported for subjects with the C9orf72 expansion and included one case with pediatric onset.Discussion:This study extends the known phenotype of the C9orf72 expansion in both age at onset and movement disorder symptoms. We propose a revised clinico-genetic algorithm for the investigation of HD phenocopy patients based on these data.