A novel missense mutation in CACNA1A evaluated by in silico protein modeling is associated with non-episodic spinocerebellar ataxia with slow progression

Katrin Bürk, Frank J. Kaiser, Stephanie Tennstedt, Ludger Schöls, Friedmar R. Kreuz, Thomas Wieland, Tim M. Strom, Thomas Büttner, Ronja Hollstein, Diana Braunholz, Jens Plaschke, Gabriele Gillessen-Kaesbach, Christine Zühlke*

*Corresponding author for this work
7 Citations (Scopus)

Abstract

Spinocerebellar ataxia type 6 (SCA6), episodic ataxia type 2 (EA2) and familial hemiplegic migraine type 1 (FHM1) are allelic disorders of the gene CACNA1A encoding the P/Q subunit of a voltage gated calcium channel. While SCA6 is related to repeat expansions affecting the C-terminal part of the protein, EA2 and FHM phenotypes are usually associated with nonsense and missense mutations leading to impaired channel properties.In three unrelated families with dominant cerebellar ataxia, symptoms cosegregated with CACNA1A missense mutations of evolutionary highly conserved amino acids (exchanges p.E668K, p.R583Q and p.D302N). To evaluate pathogenic effects, in silico, protein modeling analyses were performed which indicate structural alterations of the novel mutation p.E668K within the homologous domain 2 affecting CACNA1A protein function. The phenotype is characterised by a very slowly progressive ataxia, while ataxic episodes or migraine are uncommon. These findings enlarge the phenotypic spectrum of CACNA1A mutations.

Original languageEnglish
JournalEuropean Journal of Medical Genetics
Volume57
Issue number5
Pages (from-to)207-211
Number of pages5
ISSN1769-7212
DOIs
Publication statusPublished - 01.01.2014

Fingerprint

Dive into the research topics of 'A novel missense mutation in CACNA1A evaluated by in silico protein modeling is associated with non-episodic spinocerebellar ataxia with slow progression'. Together they form a unique fingerprint.

Cite this