Involvement of the CACNA1A gene containing region on 19p13 in migraine with and without aura

Objective: To assess the involvement of the 19p13 familial hemiplegic migra ine (FHM) locus in migraine with and without aura. Background: Migraine wit h and without aura are likely to be polygenetic multifactorial disorders. F HM is a rare dominantly inherited type of migraine with aura. In about 50% of families, FHM is caused by mutations in the P/Q-type calcium channel alp ha (1A)-subunit (CACNA1A) gene on chromosome 19p13. The CACNA1A gene is thu s a good candidate gene for "nonhemiplegic" migraine with or without aura. Methods: The authors performed an affected sibpair analysis using flanking and CACNA1A intragenic markers. The authors assessed the occurrence of shar ed parental marker alleles among 189 affected siblings from 36 extended fam ilies with typical migraine with or without aura. Results: Sibling pairs wi th any form of migraine had inherited the same 19p13 CACNA1A-containing reg ion significantly more frequently than expected by chance (maximum multipoi nt lod score = 1.22. This result. was almost exclusively dependent on the i ncreased sharing found in sibling pairs with migraine with aura (maximum mu ltipoint lod score = 1.41). The locus-specific relative risk for a sibling (lambda (s)) to suffer from migraine with aura, defined as the increase in risk of the trait attributable to the 19p13 locus, was lambda (s) = 1.56. W hen combining migraine with and without aura, lambda (s) was 1.22. Conclusi ons: The increased allele sharing in the CACNA1A gene region on 19p13 is co nsistent with an important involvement of this region in migraine, especial ly migraine with aura.