Genetic analysis of 27 Spanish patients with hemiplegic migraine, basilar-type migraine and childhood periodic syndromes.
Familial hemiplegic migraine (FHM) is a rare type of migraine with aura. Mutations in three genes have been described in FHM patients: CACNA1A (FHM1), ATP1A2 (FHM2) and SCN1A (FHM3). We screened 27 Spanish patients with hemiplegic migraine (HM), basilar-type migraine or childhood periodic syndromes (CPS) for mutations in these three genes. Two novel CACNA1A variants, p.Val581Met and p.Tyr1245Cys, and a previously annotated change, p.Cys1534Ser, were identified in individuals with HM, although they have not yet been proven to be pathogenic. Interestingly, p.Tyr1245Cys was detected in a patient displaying a changing, age-specific phenotype that began as benign paroxysmal torticollis of infancy, evolving into benign paroxysmal vertigo of childhood and later becoming HM. This is the first instance of a specific non-synonymous base change being described in a subject affected with CPS. The fact that the molecular screen identified non-synonymous changes in < 15% of our HM patients further stresses the genetic heterogeneity underlying the presumably monogenic forms of migraine.
Cuenca-León
E
E
Grup de Recerca en Neurologia Infantil i Psiquiatria Genètica, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
Corominas
R
R
Fernàndez-Castillo
N
N
Volpini
V
V
Del Toro
M
M
Roig
M
M
Macaya
A
A
Cormand
B
B
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D015220:Calcium Channels / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020325:Migraine with Aura / Q000235:genetics*; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics; D010375:Pedigree; D010507:Periodicity; D015222:Sodium Channels / Q000235:genetics; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics; D013030:Spain; D014103:Torticollis / Q000235:genetics; D014717:Vertigo / Q000235:genetics; D020864:Calcium Channels, N-Type
D015220:Calcium Channels; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D015222:Sodium Channels; D000254:Sodium-Potassium-Exchanging ATPase; C105656:CACNA1A protein, human; D020864:Calcium Channels, N-Type; C568242:SCN1A protein, human; C498531:ATP1A2 protein, human