RT Journal Article SR Electronic T1 Large scale calcium channel gene rearrangements in episodic ataxia and hemiplegic migraine: implications for diagnostic testing JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 786 OP 791 DO 10.1136/jmg.2009.067967 VO 46 IS 11 A1 R W Labrum A1 S Rajakulendran A1 T D Graves A1 L H Eunson A1 R Bevan A1 M G Sweeney A1 S R Hammans A1 N Tubridy A1 T Britton A1 L J Carr A1 J R Ostergaard A1 C R Kennedy A1 A Al-Memar A1 D M Kullmann A1 S Schorge A1 K Temple A1 M B Davis A1 M G Hanna YR 2009 UL http://jmg.bmj.com/content/46/11/786.abstract AB 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.