Familial Hemiplegic Migraine and Episodic Ataxia type-2 Are Caused by Mutations in the Ca2+ Channel Gene CACNL1A4

Cell. 1996 Nov 1;87(3):543-52. doi: 10.1016/s0092-8674(00)81373-2.

Abstract

Genes for familial hemiplegic migraine (FHM) and episodic ataxia type-2 (EA-2) have been mapped to chromosome 19p13. We characterized a brain-specific P/Q-type Ca2+ channel alpha1-subunit gene, CACNL1A4, covering 300 kb with 47 exons. Sequencing of all exons and their surroundings revealed polymorphic variations, including a (CA)n-repeat (D19S1150), a (CAG)n-repeat in the 3'-UTR, and different types of deleterious mutations in FHM and EA-2. In FHM, we found four different missense mutations in conserved functional domains. One mutation has occurred on two different haplotypes in unrelated FHM families. In EA-2, we found two mutations disrupting the reading frame. Thus, FHM and EA-2 can be considered as allelic channelopathies. A similar etiology may be involved in common types of migraine.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Base Sequence
  • Calcium Channels / chemistry
  • Calcium Channels / genetics*
  • Cerebellar Ataxia / genetics*
  • Cerebellar Ataxia / physiopathology
  • Chromosome Mapping
  • Chromosomes, Human, Pair 19 / genetics
  • Cortical Spreading Depression / genetics
  • DNA Mutational Analysis
  • Female
  • Hemiplegia / etiology*
  • Humans
  • Male
  • Migraine Disorders / classification
  • Migraine Disorders / complications
  • Migraine Disorders / genetics*
  • Migraine Disorders / physiopathology
  • Models, Molecular
  • Molecular Sequence Data
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / genetics*
  • Pedigree
  • Point Mutation
  • Polymorphism, Single-Stranded Conformational
  • Sequence Deletion

Substances

  • Calcium Channels
  • Nerve Tissue Proteins

Associated data

  • GENBANK/X99897
  • GENBANK/Z80114
  • GENBANK/Z80115