18p 染色体上的 DYT7 基因座与颈性肌张力障碍的关系值得怀疑。
DYT7 gene locus for cervical dystonia on chromosome 18p is questionable.
机构信息
Institute of Human Genetics, Justus Liebig University, Giessen, Germany.
出版信息
Mov Disord. 2012 Dec;27(14):1819-21. doi: 10.1002/mds.25219. Epub 2012 Oct 31.
BACKGROUND
A locus implicated in autosomal dominant cervical dystonia was assigned to chromosome 18p in 1 large family more than 15 years ago. This locus was designated DYT7. We reanalyzed the family clinically and genetically.
METHODS
Clinical reevaluation of all family members was performed. There was Sanger sequencing of candidate genes, SNP array analysis, and exome sequencing in definitely affected family members.
RESULTS
Diagnosis of cervical dystonia was definite in 6 family members and possible in 12. Analysis of candidate genes in 18p revealed no alteration in definitely affected patients. There was no disease causing copy number variant in 18p. No potentially disease-causing mutations were detected in 18p by exome sequencing. The CIZ1 gene, mutated in some cases of cervical dystonia, was excluded.
CONCLUSIONS
Location of DYT7 on 18p in autosomal dominant cervical dystonia is questionable. We demonstrate genetic heterogeneity of this form of dystonia.
背景
15 多年前，一个常染色体显性遗传性颈部肌张力障碍的基因座被定位于 18 号染色体 p 臂，该基因座被命名为 DYT7。我们对该家族进行了临床和遗传学的重新分析。
方法
对所有家族成员进行了临床再评估。对明确受影响的家族成员进行了 Sanger 测序、SNP 芯片分析和外显子组测序。
结果
6 名家族成员的颈部肌张力障碍诊断明确，12 名家族成员的颈部肌张力障碍诊断可能。对 18p 上的候选基因分析显示，明确受影响的患者没有改变。18p 上没有致病拷贝数变异。外显子组测序未发现 18p 上潜在的致病突变。CIZ1 基因在一些颈部肌张力障碍病例中发生突变，已被排除在外。
结论
常染色体显性遗传性颈部肌张力障碍的 DYT7 定位于 18p 是值得怀疑的。我们证明了这种形式的肌张力障碍存在遗传异质性。
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