Mutations in HPCA cause autosomal-recessive primary isolated dystonia.
Mutations in HPCA cause autosomal-recessive primary isolated dystonia.
复制标题
DOI：
10.1016/j.ajhg.2015.02.007
复制
发表时间：
2015-04-02
影响因子：
9.8
通讯作者：
Wood NW
中科院分区：
文献类型：
--
作者：
Charlesworth G;Angelova PR;Bartolomé-Robledo F;Ryten M;Trabzuni D;Stamelou M;Abramov AY;Bhatia KP;Wood NW
有关以常染色体隐性遗传(AR)方式遗传的原发性孤立肌张力障碍的报道，通常被归类为“DYT2肌张力障碍”，几十年来一直在科学文献中出现，但迄今尚未确定遗传原因。利用纯合性图谱和全外显子组测序相结合的方法，我们在一个受AR孤立肌张力障碍影响的近亲家庭中发现了HPCA的纯合子突变，HPCA是一种编码神经元钙感受器蛋白的基因，几乎只在大脑中发现，在纹状体中水平特别高，是该家族的致病原因。随后，在受AR孤立肌张力障碍影响的第二个独立家系中，也发现了HPCA的复合杂合子突变。功能研究表明，海马素可能在调节电压依赖性钙通道中发挥作用。确定HPCA突变是AR原发孤立肌张力障碍的原因，为进一步研究“DYT2肌张力障碍”是否为遗传同质性疾病铺平了道路。
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.
登录
查看更多内容
影响因子：
4
作者：
Suwanjang W;Holmström KM;Chetsawang B;Abramov AY
通讯作者：
Abramov AY
影响因子：
11.2
作者：
Lohmann K;Wilcox RA;Winkler S;Ramirez A;Rakovic A;Park JS;Arns B;Lohnau T;Groen J;Kasten M;Brüggemann N;Hagenah J;Schmidt A;Kaiser FJ;Kumar KR;Zschiedrich K;Alvarez-Fischer D;Altenmüller E;Ferbert A;Lang AE;Münchau A;Kostic V;Simonyan K;Agzarian M;Ozelius LJ;Langeveld AP;Sue CM;Tijssen MA;Klein C
通讯作者：
Klein C
影响因子：
2.2
作者：
Chouery, E.;Kfoury, J.;Megarbane, A.
通讯作者：
Megarbane, A.
影响因子：
9.9
作者：
Khan, NL;Wood, NW;Bhatia, KP
通讯作者：
Bhatia, KP
影响因子：
30.8
作者：
Fuchs, Tania;Gavarini, Sophie;Ozelius, Laurie J.
通讯作者：
Ozelius, Laurie J.