Molecular analysis on migraine patients: exclusion of mutations in cacnli A4 gene

A gene for Familial Hémiplégie Migraine (FHM) has been assigned to chromosome 19pl3 in about 50% of the families tested (Jountd A et al, Nat Genet 1993; 5:40-45). Recently (Ophoff RA et al, Cell 1996; 87: 543-552) 4 point mutations in the CACNL1A4 gene were identified in 5 unrelated FHM families, from different countries. The molecular mechanisms of these mutations are- unknown. FHM is considered a subtype of migraine with aura including hemiparesis and where at least one first degree relative has identical attacks. We investigated wether other kinds of migraine could be considered as different clinical manifestations of this same genetic defect. We gathered 6 patients with FHM, 1 with basilar migraine, 1 affected by migraine with prolonged aura, 12 with familiar migraine with aura, and 15 sporadic cases of migrainous infarction, from different Italian regions. All the patients were diagnosed according to IHS criteria. Molecular analysis was performed searching for the mutation in CACNLI A4 gene, particularly in exon 4 (G→A at nt 850), 17 (T→C at nt 2416) and 36 (A->C at nt 5706).AII the investigations were negative. Our data confirm the genetic heterogeneity of FHM, but give no further information on migraine.