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Large scale calcium channel gene rearrangements in episodic ataxia and hemiplegic migraine: implications for diagnostic testing

Labrum, RW and Rajakulendran, S and Graves, TD and Eunson, LH and Bevan, R and Sweeney, MG and Hammans, SR and Tubridy, N and Britton, T and Carr, LJ and Ostergaard, JR and Kennedy, CR and Al-Memar, A and Kullmann, DM and Schorge, S and Temple, K and Davis, MB and Hanna, MG (2009) 'Large scale calcium channel gene rearrangements in episodic ataxia and hemiplegic migraine: implications for diagnostic testing.' Journal of Medical Genetics, 46 (11). pp. 786-791. ISSN 0022-2593

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Abstract

Background: Episodic ataxia type 2 (EA2) and familial hemiplegic migraine type 1 (FHM1) are autosomal dominant disorders characterised by paroxysmal ataxia and migraine, respectively. Point mutations in CACNA1A, which encodes the neuronal P/Q-type calcium channel, have been detected in many cases of EA2 and FHM1. The genetic basis of typical cases without CACNA1A point mutations is not fully known. Standard DNA sequencing methods may miss large scale genetic rearrangements such as deletions and duplications. The authors investigated whether large scale genetic rearrangements in CACNA1A can cause EA2 and FHM1. Methods: The authors used multiplex ligation dependent probe amplification (MLPA) to screen for intragenic CACNA1A rearrangements. Results: The authors identified five previously unreported large scale deletions in CACNA1A in seven families with episodic ataxia and in one case with hemiplegic migraine. One of the deletions (exon 6 of CACNA1A) segregated with episodic ataxia in a four generation family with eight affected individuals previously mapped to 19p13. In addition, the authors identified the first pathogenic duplication in CACNA1A in an index case with isolated episodic diplopia without ataxia and in a first degree relative with episodic ataxia. Conclusions: Large scale deletions and duplications can cause CACNA1A associated channelopathies. Direct DNA sequencing alone is not sufficient as a diagnostic screening test.

Item Type: Article
Subjects: Q Science > QH Natural history > QH426 Genetics
R Medicine > R Medicine (General)
Divisions: Faculty of Science and Health
Faculty of Science and Health > Life Sciences, School of
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 11 Jan 2013 14:58
Last Modified: 06 Jan 2022 13:40
URI: http://repository.essex.ac.uk/id/eprint/5063

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