Details

Autor(en) / Beteiligte

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

Titel

Mutations in HPCA Cause Autosomal-Recessive Primary Isolated Dystonia

Ist Teil von

• American journal of human genetics, 2015-04, Vol.96 (4), p.657-665

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.