Mutations in CIZ1 cause adult onset primary cervical dystonia.
Mutations in CIZ1 cause adult onset primary cervical dystonia.
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DOI：
10.1002/ana.23547
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发表时间：
2012-04
影响因子：
11.2
通讯作者：
LeDoux, Mark S.
中科院分区：
文献类型：
--
作者：
Xiao, Jianfeng;Uitti, Ryan J.;Zhao, Yu;Vemula, Satya R.;Perlmutter, Joel S.;Wszolek, Zbigniew K.;Maraganore, Demetrius M.;Auburger, Georg;Leube, Barbara;Lehnhoff, Katja;LeDoux, Mark S.
Primary dystonia is usually of adult onset, can be familial, and frequently involves the cervical musculature. Our goal was to identify the causal mutation in a family with adult-onset, primary cervical dystonia. Linkage and haplotype analyses were combined with solution-based whole-exome capture and massively parallel sequencing in a large Caucasian pedigree with adult-onset, primary cervical dystonia to identify a cosegregating mutation. High-throughput screening and Sanger sequencing were completed in 308 Caucasians with familial or sporadic adult-onset cervical dystonia and matching controls for sequence variants in this mutant gene. Exome sequencing led to the identification of an exonic splicing enhancer mutation in Exon 7 of CIZ1 (c.790A>G, p.S264G) which encodes CIZ1, Cip1-interacting zinc finger protein 1. CIZ1 is a p21Cip1/Waf1-interacting zinc finger protein expressed in brain and involved in DNA synthesis and cell-cycle control. Using a minigene assay, we showed that c.790A>G altered CIZ1 splicing patterns. The p.S264G mutation also altered the nuclear localization of CIZ1. Screening in subjects with adult-onset cervical dystonia identified two additional CIZ1 missense mutations (p.P47S and p.R672M). Mutations in CIZ1 may cause adult-onset, primary cervical dystonia, possibly by precipitating neurodevelopmental abnormalities that manifest in adults and/or G1/S cell-cycle dysregulation in the mature central nervous system.
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影响因子：
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作者：
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通讯作者：
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