Multiple-system atrophy is genetically distinct from identified inherited causes of spinocerebellar degeneration

被引:26
作者
Bandmann, O
Sweeney, MG
Daniel, SE
Wenning, GK
Quinn, N
Marsden, CD
Wood, NW
机构
[1] Univ London, Dept Clin Neurol, Inst Neurol, London WC1N 3BG, England
[2] Parkinsons Dis Soc, Brain Bank, London, England
关键词
D O I
10.1212/WNL.49.6.1598
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Multiple system atrophy (MSA) is a neurodegenerative disorder of unknown cause. The only case-control study conducted in MSA patients to date suggested a possible contributory genetic component in the pathogenesis of this disorder. The aim of this study was to evaluate a possible overlap between clinically or pathologically well-defined MSA and other conditions with an identified genetic defect causing spinocerebellar degeneration in humans or mutant mice strains. The spinocerebellar ataxia type 1 and 3 genes (SCA1 and SCA3) were analyzed for a pathologic expansion in 80 patients with MSA to evaluate a possible overlap between MSA and SCA1 or SCA3. Weaver mice and lurcher mice are animal models for spinocerebellar degeneration; both share pathologic features with MSA. We sequenced the 115 pore region of the human homologue of the weaver mouse gene, hiGIRK2, in all our patients. In lurcher mice, previous biochemical studies have shown a decreased intracellular response to insulin-like growth factor 1 (IGF-1) in the cerebellar cortex, and we thus investigated the possibility of an allelic association between MSA and the receptor for IGF-1. In addition, we evaluated a possible involvement of the ciliary neurotrophic factor gene (CNTF) and examined the role of HLA-A32 to clarify the conflicting data from previous studies. No changes were detected in any of the analyzed genes. Our studies strongly suggest that MSA is an autonomous syndrome distinct from identified genetic causes for spinocerebellar degeneration.
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页码:1598 / 1604
页数:7
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