Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA,
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
Neurodegener Dis. 2018;18(5-6):239-253. doi: 10.1159/000492499. Epub 2018 Oct 18.
European studies identified the C9orf72 repeat expansion as the most frequent genetic alteration in patients with Huntington disease (HD)-like phenotypes but negative HD genetic testing.
To investigate C9orf72 repeat expansion frequency in individuals tested for HD in a North American tertiary referral laboratory.
Three hundred and seventy-three cases (115 positive and 258 negative for HD) were evaluated by genotyping PCR, with follow-up Southern blot and 5' repeat methylation status assessment by combined repeat-primed and methylation-specific PCR in a subset.
Three cases (all HD-negative) tested positive: 2 had > 2,000 repeats and were methylated, 1 had 80-100 repeats and was unmethylated. Two cases (1 HD-positive and 1 HD-negative) had intermediate alleles (20-29 repeats) and were unmethylated. The remaining 368 cases were negative (< 20 repeats). C9orf72 repeat expansion was absent in patients with HD and was identified in a small subset (1.2%) of patients with negative HD genetic testing.
These findings suggest that C9orf72 repeat expansion does not coexist with HTT repeat expansion and that C9orf72 repeat expansion testing is unnecessary for patients with HD. In addition, C9orf72 evaluation may be considered for individuals negative for HD genetic testing. Similar to in previous studies, methylation of C9orf72 repeat expansion was limited to large expansions.
欧洲的研究表明，在具有亨廷顿病（HD）样表型但 HD 基因检测呈阴性的患者中，C9orf72 重复扩展是最常见的遗传改变。
调查在北美三级转诊实验室中对 HD 进行检测的个体中 C9orf72 重复扩展的频率。
通过基因分型 PCR 对 373 例病例（115 例阳性和 258 例阴性）进行评估，对亚组进行 Southern 印迹和 5'重复甲基化状态评估的重复引物和甲基化特异性 PCR。
有 3 例（均为 HD 阴性）呈阳性：2 例重复>2000 次且甲基化，1 例重复 80-100 次且未甲基化。2 例（1 例 HD 阳性和 1 例 HD 阴性）具有中间等位基因（20-29 次重复）且未甲基化。其余 368 例为阴性（<20 次重复）。C9orf72 重复扩展不存在于 HD 患者中，在一小部分（1.2%）HD 基因检测阴性的患者中被发现。
这些发现表明，C9orf72 重复扩展不会与 HTT 重复扩展共存，并且 C9orf72 重复扩展检测对于 HD 患者是不必要的。此外，对于 HD 基因检测阴性的个体，可以考虑进行 C9orf72 评估。与之前的研究相似，C9orf72 重复扩展的甲基化仅限于大的扩展。
