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From the Department of Neurology (Drs. Terwindt, Ophoff, Haan, and Ferrari, and M.N. Vergouwe) and MGC–Department of Human and Clinical Genetics (Drs. Ophoff, Frants, and Sandkuijl and R. van Eijk and M.N. Vergouwe), Leiden University Medical Centre; Rijnland Hospital (Dr. Haan), Leiderdorp; and MGC–Department of Clinical Genetics (Dr. Sandkuijl), Erasmus University Rotterdam, the Netherlands.
Address correspondence and reprint requests to Dr. M.D. Ferrari, Department of Neurology, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, The Netherlands; e-mail: M.D.Ferrari{at}lumc.nl
OBJECTIVE: To assess the involvement of the 19p13 familial hemiplegic migraine (FHM) locus in migraine with and without aura.
BACKGROUND: Migraine with and without aura are likely to be polygenetic multifactorial disorders. FHM 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 
1A-subunit (CACNA1A) gene on chromosome 19p13. The CACNA1A gene is thus 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 shared parental marker alleles among 189 affected siblings from 36 extended families with typical migraine with or without aura.
RESULTS: Sibling pairs with any form of migraine had inherited the same 19p13 CACNA1A-containing region significantly more frequently than expected by chance (maximum multipoint lod score = 1.22). This result was almost exclusively dependent on the increased sharing found in sibling pairs with migraine with aura (maximum multipoint lod score = 1.41). The locus-specific relative risk for a sibling (
s) to suffer from migraine with aura, defined as the increase in risk of the trait attributable to the 19p13 locus, was s = 1.56. When combining migraine with and without aura, s was 1.22.
CONCLUSIONS: The increased allele sharing in the CACNA1A gene region on 19p13 is consistent with an important involvement of this region in migraine, especially migraine with aura.
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