Two novel families with hemiplegic migraine caused by recurrent SCN1A mutation p.F1499L

Cephalalgia. 2018 Jul;38(8):1503-1508. doi: 10.1177/0333102417742365. Epub 2017 Nov 16.

Abstract

Background Familial hemiplegic migraine type 3 is a monogenic subtype of migraine caused by missense mutations in the neuronal voltage-gated sodium channel gene SCN1A, with 10 different mutations reported so far. In two familial hemiplegic migraine type 3 families, partial cosegregation with a rare eye phenotype (elicited repetitive daily blindness) was previously reported. Methods Two novel familial hemiplegic migraine pedigrees were subjected to genetic analysis and detailed work-up of associated clinical features. Results In both pedigrees, we identified SCN1A mutation p.F1499L, which has been previously associated with familial hemiplegic migraine type 3 and elicited repetitive daily blindness. Both families displayed a pure familial hemiplegic migraine phenotype without evidence of an episodic eye phenotype. Conclusion Like a substantial proportion of other familial hemiplegic migraine type 3 mutations, p.F1499L affects the intracellular linker between domains III and IV of SCN1A, which seems to be a mutational hot-spot. Our new data establish p.F1499L as a recurrent familial hemiplegic migraine type 3 mutation. Elicited repetitive daily blindness seems to be a rare phenomenon in familial hemiplegic migraine type 3, even in carriers of the same mutation.

Keywords: Migraine; SCN1A; elicited repetitive daily blindness; genetics; hemiplegic migraine; mutation.

Publication types

  • Letter

MeSH terms

  • Adult
  • Aged
  • Chromosomes, Human, Pair 2 / genetics*
  • Croatia
  • Family
  • Female
  • Genetic Testing
  • Germany
  • Humans
  • Male
  • Middle Aged
  • Migraine Disorders / genetics*
  • Mutation, Missense
  • NAV1.1 Voltage-Gated Sodium Channel / genetics*
  • Pedigree
  • Phenotype
  • Rare Diseases / genetics*

Substances

  • NAV1.1 Voltage-Gated Sodium Channel
  • SCN1A protein, human

Supplementary concepts

  • Migraine, Familial Hemiplegic, 3