Jih Kang-Yang, Lai Kuan-Lin, Lin Kon-Ping, Liao Yi-Chu, Lee Yi-Chung
Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
Department of Physiology, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan, ROC.
J Chin Med Assoc. 2023 Jan 1;86(1):47-51. doi: 10.1097/JCMA.0000000000000837. Epub 2022 Nov 28.
Expanded HTT alleles with 40 or more CAG repeats were recently found to be a rare cause of frontotemporal dementia and amyotrophic lateral sclerosis (ALS) spectrum diseases. The aim of this study was to investigate the role of HTT repeat expansions in a Taiwanese cohort with ALS.
We analyzed the numbers of CAG repeats in exon 1 of HTT in a cohort of 410 Taiwanese patients with ALS and 1514 control individuals by utilizing polymerase chain reaction and amplicon fragment length analysis.
Only one of the 410 ALS patients carried a reduced-penetrance HD-causing allele with 39 CAG repeats, and none had an expanded HTT CAG repeats ≥40. The patient presented with rapidly progressive bulbar-onset ALS with disease onset at the age of 64 years. He had neither chorea nor cognitive impairment. He had a family history of chorea, but no other family member manifested with ALS. None of the 1514 control individuals carried an HTT expanded allele with CAG repeats larger than 37 repeats.
The HTT allele with 39 CAG repeats could be a genetic factor linked to ALS susceptibility.
最近发现，含有40个或更多CAG重复序列的扩展型亨廷顿蛋白（HTT）等位基因是额颞叶痴呆和肌萎缩侧索硬化（ALS）谱系疾病的罕见病因。本研究旨在调查HTT重复序列扩展在台湾ALS队列中的作用。
我们利用聚合酶链反应和扩增子片段长度分析，分析了410名台湾ALS患者和1514名对照个体的HTT外显子1中CAG重复序列的数量。
410例ALS患者中只有1例携带导致亨廷顿舞蹈症（HD）的低外显率等位基因，其CAG重复序列为39个，没有患者的HTT CAG重复序列扩展≥40。该患者表现为快速进展的延髓起病型ALS，发病年龄为64岁。他既没有舞蹈症也没有认知障碍。他有舞蹈症家族史，但没有其他家庭成员患有ALS。1514名对照个体中，没有一个携带CAG重复序列大于37个的HTT扩展等位基因。
含有39个CAG重复序列的HTT等位基因可能是与ALS易感性相关的遗传因素。
