CACNA1B mutation is linked to unique myoclonus-dystonia syndrome.

Article Details

Citation

Groen JL, Andrade A, Ritz K, Jalalzadeh H, Haagmans M, Bradley TE, Jongejan A, Verbeek DS, Nurnberg P, Denome S, Hennekam RC, Lipscombe D, Baas F, Tijssen MA

CACNA1B mutation is linked to unique myoclonus-dystonia syndrome.

Hum Mol Genet. 2015 Feb 15;24(4):987-93. doi: 10.1093/hmg/ddu513. Epub 2014 Oct 8.

PubMed ID
25296916 [ View in PubMed
]
Abstract

Using exome sequencing and linkage analysis in a three-generation family with a unique dominant myoclonus-dystonia-like syndrome with cardiac arrhythmias, we identified a mutation in the CACNA1B gene, coding for neuronal voltage-gated calcium channels CaV2.2. This mutation (c.4166G>A;p.Arg1389His) is a disruptive missense mutation in the outer region of the ion pore. The functional consequences of the identified mutation were studied using whole-cell and single-channel patch recordings. High-resolution analyses at the single-channel level showed that, when open, R1389H CaV2.2 channels carried less current compared with WT channels. Other biophysical channel properties were unaltered in R1389H channels including ion selectivity, voltage-dependent activation or voltage-dependent inactivation. CaV2.2 channels regulate transmitter release at inhibitory and excitatory synapses. Functional changes could be consistent with a gain-of-function causing the observed hyperexcitability characteristic of this unique myoclonus-dystonia-like syndrome associated with cardiac arrhythmias.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Voltage-dependent N-type calcium channel subunit alpha-1BQ00975Details