FAMILIAL TYPICAL MIGRAINE - LINKAGE TO CHROMOSOME 19P13 AND EVIDENCE FOR GENETIC-HETEROGENEITY

Migraine is a frequent familial disorder that, in common with most mul tifactorial disorders, has an unknown etiology. The authors identified several families with multiple individuals affected by typical migrai ne using a single set of diagnostic criteria and studied these familie s for cosegregation between the disorder and markers on chromosome 19, the location of a mutation that causes a rare form of familial hemipl egic migraine (FHM). One large tested family showed both cosegregation and significant allele sharing for markers situated within or adjacen t to the FHM locus. Multipoint GENEHUNTER results indicated significan t excess allele sharing across a 12.6-cM region containing the FHM Ca2 + channel gene, CACNL1A4 (maximum nonparametric linkage Z score = 6.64 , p = 0.0026), with a maximum parametric lod score of 1.92 obtained fo r a (CAG)(n) triplet repeat polymorphism situated in exon 47 of this g ene. The CAG expansion did not, however, appear to be the cause of mig raine in this pedigree. Other tested families showed neither cosegrega tion nor excess allele sharing to chromosome 19 markers. HOMOG analysi s indicated heterogeneity, generating a maximum HLOD score of 3.6. It was concluded that Chr19 mutations either in the CACNL1A4 gene or a cl osely linked gene are implicated in some pedigrees with familial typic al migraine, and that the disorder is genetically heterogeneous.