南斯拉夫8型脊髓小脑共济失调重复序列扩张的遗传学与临床分析。

Genetic and clinical analysis of spinocerebellar ataxia type 8 repeat expansion in Yugoslavia.

作者信息

Topisirovic I, Dragasevic N, Savic D, Ristic A, Keckarevic M, Keckarevic D, Culjkovic B, Petrovic I, Romac S, Kostic V S

机构信息

PCR Center, Faculty for Biology, Institute of Neurology CCS, School of Medicine, University of Belgrade, Serbia.

出版信息

Clin Genet. 2002 Oct;62(4):321-4. doi: 10.1034/j.1399-0004.2002.620412.x.

DOI:10.1034/j.1399-0004.2002.620412.x

PMID:12372061

Abstract

Spinocerebellar ataxia type 8 (SCA8) is a slowly progressive ataxia causally associated with untranslated CTG repeat expansion on chromosome 13q21. However, the role of the CTG repeat in SCA8 pathology is not yet well understood. Therefore, we studied the length of the SCA8 CTA/CTG expansions (combined repeats, CRs) in 115 patients with ataxia, 64 unrelated individuals with non-triplet neuromuscular diseases, 70 unrelated patients with schizophrenia, and 125 healthy controls. Only one patient with apparently sporadic ataxia was identified with an expansion of 100 CRs. He had inherited the expansion from his asymptomatic father (140 CRs) and transmitted the mutation to his son (92 CRs). Paternal transmission in this family produced contractions of 40 and 8 CRs, respectively. None of the subjects from other studied groups had an expansion at the SCA8 locus. In the control group the number of CRs at the SCA8 locus ranged from 14 to 34. Our findings support the notion that allelic variants of the expansion mutation at the SCA8 locus can predispose to ataxia.

摘要

8型脊髓小脑共济失调（SCA8）是一种缓慢进展的共济失调，与13q21染色体上未翻译的CTG重复序列扩增存在因果关系。然而，CTG重复序列在SCA8病理中的作用尚未完全明确。因此，我们研究了115例共济失调患者、64例非三联体神经肌肉疾病的无关个体、70例精神分裂症无关患者和125例健康对照者中SCA8 CTA/CTG扩增（联合重复序列，CRs）的长度。仅1例明显散发型共济失调患者被鉴定出有100个CRs的扩增。他从无症状的父亲（140个CRs）那里遗传了该扩增，并将该突变遗传给了他的儿子（92个CRs）。在这个家族中，父系传递分别导致了40个和8个CRs的收缩。其他研究组的受试者在SCA8位点均无扩增。在对照组中，SCA8位点的CRs数量范围为14至34。我们的研究结果支持这样一种观点，即SCA8位点的扩增突变等位基因变异可能易患共济失调。