Referenced in: none

Automatically associated channels: Cav2.1

Title: Mutations in HPCA cause autosomal-recessive primary isolated dystonia.

Authors: Gavin Charlesworth, Plamena R Angelova, Fernando Bartolomé-Robledo, Mina Ryten, Daniah Trabzuni, Maria Stamelou, Andrey Y Abramov, Kailash P Bhatia, Nicholas W Wood

Journal, date & volume: Am. J. Hum. Genet., 2015 Apr 2 , 96, 657-65

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/25799108

Abstract
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.