CACNA1A R1347Q: a frequent recurrent mutation in hemiplegic migraine

• Published in: Clinical genetics Vol. 74; no. 5; pp. 481 - 485
• Main Authors: Stam, AH, Vanmolkot, KRJ, Kremer, HPH, Gärtner, J, Brown, J, Leshinsky-Silver, E, Gilad, R, Kors, EE, Frankhuizen, WS, Ginjaar, HB, Haan, J, Frants, RR, Ferrari, MD, Van Den Maagdenberg, AMJM, Terwindt, GM
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-11-2008; Blackwell
• Subjects: Adolescent; Aged; Biological and medical sciences; CACNA1A; calcium channel; Calcium Channels - genetics; DNA Mutational Analysis; familial hemiplegic migraine; Female; Fundamental and applied biological sciences. Psychology; General aspects. Genetic counseling; Genes; Genetic disorders; Genetics of eukaryotes. Biological and molecular evolution; Genotype; Haplotypes; Humans; Male; Medical genetics; Medical sciences; Middle Aged; Migraine; Migraine with Aura - genetics; Models, Biological; Molecular and cellular biology; Mutation; Nervous system (semeiology, syndromes); Nervous system as a whole; Neurology; Pedigree; Phenotype; phenotype comparison; Human; calcium channel; Familial hemiplegic migraine; Nervous system diseases; Relapse; Typing; Motor system disorder; Genotype; Ionic channel; Recurrent; Phenotype; Calcium ion; Genetics; Hemiplegia; CACNA 1A; phenotype comparison; Mutation; Neurological disorder; Comparative study
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1111/j.1399-0004.2008.00996.x

Of the 18 missense mutations in the CACNA1A gene, which are associated with familial hemiplegic migraine type 1 (FHM1), only mutations S218L, R583Q and T666M were identified in more than two independent families. Including the four novel families presented here, of which two represent de novo cases, the R1347Q mutation has now been identified in six families. A genotype–phenotype comparison of R1347Q mutation carriers revealed a wide clinical spectrum ranging from (trauma triggered) hemiplegic migraine with and without ataxia, loss of consciousness and epilepsy. R1347Q is the third most frequent mutation in hemiplegic migraine patients and should therefore be screened with priority for confirmation of clinical diagnosis. This study clearly demonstrates that the availability of multiple families better reflects the full clinical spectrum associated with FHM1 mutations.