Next generation sequencing identifies novel CACNA1A gene mutations in Episodic Ataxia type 2

Maksemous, Neven, Roy, Bishakha, Smith, Robert A., & Griffiths, Lyn R. (2016) Next generation sequencing identifies novel CACNA1A gene mutations in Episodic Ataxia type 2. Molecular Genetics and Genomic Medicine, 4(2), pp. 211-222.

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Episodic Ataxia type 2 (EA2) is a rare autosomal dominantly inherited neurological disorder characterized by recurrent disabling imbalance, vertigo and episodes of ataxia lasting minutes to hours. EA2 is caused most often by loss of function mutations of the calcium channel gene CACNA1A. In addition to EA2, mutations in CACNA1A are responsible for two other allelic disorders: familial hemiplegic migraine type1 (FHM1) and spinocerebellar ataxia type 6 (SCA6). Herein, we have utilised Next Generation Sequencing (NGS) to screen the coding sequence, exon-intron boundaries and UTRs of five genes where mutation is known to produce symptoms related to EA2, including CACNA1A. We performed this screening in a group of 31 unrelated patients with EA2 symptoms. Both novel and known mutations were detected through NGS technology, and confirmed through Sanger sequencing. Genetic testing showed in total 15 mutation bearing patients (48%), of which 9 were novel mutations (6 missense and 3 small frameshift deletion mutations) and six known mutations (4 missense and 2 nonsense).These results demonstrate the efficiency of our NGS-panel for detecting known and novel mutations for EA2 in the CACNA1A gene, also identifying a novel missense mutation in ATP1A2 which is not a normal target for EA2 screening.

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ID Code: 94391
Item Type: Journal Article
Refereed: Yes
Keywords: AmpliSeq Custom Panel, CACNA1A, Episodic Ataxia type 2, Next Generation Sequencing.
DOI: 10.1002/mgg3.196
ISSN: 2324-9269
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: 2016 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.
Copyright Statement: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Deposited On: 05 Apr 2016 04:17
Last Modified: 09 Apr 2016 04:12

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