期刊
AMERICAN JOURNAL OF HUMAN GENETICS
卷 96, 期 4, 页码 657-665出版社
CELL PRESS
DOI: 10.1016/j.ajhg.2015.02.007
关键词
-
资金
- Medical Research Council
- Wellcome Trust [WT089698/Z/09/Z]
- Bachman-Strauss Dystonia Parkinsonism Foundation
- Department of Health's National Institute for Health Research Biomedical Research Centres
- Medical Research Council [MC_G0901330, MC_PC_09003, MC_G1000735, MR/L501554/1] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0513-10064, ACF-2012-17-017, NF-SI-0507-10376] Funding Source: researchfish
- Parkinson's UK [G-0612] Funding Source: researchfish
- MRC [MC_G0901330, MC_PC_09003, MC_G1000735] Funding Source: UKRI
Reports of primary isolated dystonia inherited in an autosomal-recessive (AR) manner, often lumped together as DYT2 dystonia, have appeared in the scientific literature for several decades, but no genetic cause has been identified to date. Using a combination of homozygosity mapping and whole-exome sequencing in a consanguineous kindred affected by AR isolated dystonia, we identified homozygous mutations in HPCA, a gene encoding a neuronal calcium sensor protein found almost exclusively in the brain and at particularly high levels in the striatum, as the cause of disease in this family. Subsequently, compound-heterozygous mutations in HPCA were also identified in a second independent kindred affected by AR isolated dystonia. Functional studies suggest that hippocalcin might play a role in regulating voltage-dependent calcium channels. The identification of mutations in HPCA as a cause of AR primary isolated dystonia paves the way for further studies to assess whether DYT2 dystonia is a genetically homogeneous condition or not.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据