A gene on SCA4 locus causes dominantly inherited pure cerebellar ataxia
A gene on SCA4 locus causes dominantly inherited pure cerebellar ataxia
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DOI：
10.1212/wnl.54.10.1971
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发表时间：
2000-05-23
期刊：
影响因子：
9.9
通讯作者：
Mizusawa, H
中科院分区：
文献类型：
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作者：
Nagaoka, U;Takashima, M;Mizusawa, H
背景：常染色体显性遗传性小脑性共济失调（ADCA）有几个不同的基因或基因位点。然而，其他类型的共济失调仍然未分配。目的：寻找ADCA的新基因位点。方法：对6个患有ADCA伴单纯小脑综合征（ADCA III型）的日本家族进行了检查。这些家族在分子水平上被排除为脊髓小脑共济失调（SCA）1 - 3型、5 - 8型和10型。进行了临床检查，并在250个微卫星DNA标记上进行了全基因组连锁搜索。结果如下：与人类染色体16 q上的标记发现了连锁的强有力证据，单倍型和多点分析进一步细化了D16 S3089和D16 S515之间的10.9 cM间隔的基因位点。在此区间内，还发现了与标记D16 S3107的连锁不平衡。该位点正好是SCA 4的候选区间，SCA 4是一种罕见的ADCA形式，临床上以共济失调伴感觉神经病和锥体束体征为特征。这表明SCA 4和我们的ADCA III型可能是具有不同临床特征的等位基因疾病。结论：本研究提供的证据表明，SCA 4位点上的基因导致一个纯粹的小脑综合征。
Background: Several different genes or their loci have been identified for autosomal dominant cerebellar ataxia (ADCA). However, other types of ataxia remain unassigned. Objective: To identify a new locus for ADCA. Methods: Six Japanese families with ADCA with pure cerebellar syndrome (ADCA type III) were examined. These families had been molecularly excluded for spinocerebellar ataxia (SCA) types 1 through 3, 5 through 8, and 10. Clinical examination was undertaken, and a genome-wide linkage search was performed on 250 microsatellite DNA markers. Results: Strong evidence for linkage was found with markers on human chromosome 16q, and haplotype and multipoint analyses further refined the gene locus in a 10.9-cM interval between D16S3089 and D16S515. Linkage disequilibrium was further found with the marker D16S3107 within the interval. The locus was exactly the candidate interval of SCA4, a rare form of ADCA clinically characterized by ataxia with sensory neuropathy anti pyramidal tract signs. This would suggest that SCA4 and our ADCA type III are likely to be allelic disorders with different clinical features. Conclusion: The current study provides evidence that a gene on the SCA4 locus causes a pure cerebellar syndrome.