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

Familial hemiplegic migraine and episodic ataxia type-2 are linked to chromosome 19p13. Researchers studied a specific gene called CACNL1A4, which forms a brain-specific calcium channel. This gene consists of 47 exons and spans 300 kb. They sequenced the exons and surrounding areas, discovering several variations. These included a (CA)n-repeat and a (CAG)n-repeat in the gene's 3'-UTR. They also identified different harmful mutations in familial hemiplegic migraine and episodic ataxia type-2. In familial hemiplegic migraine, four missense mutations were found in important functional regions. One mutation appeared in two unrelated families. In episodic ataxia type-2, two mutations disrupted the gene's reading frame. The findings suggest that familial hemiplegic migraine and episodic ataxia type-2 are related channelopathies. This research implies that similar mechanisms may also exist in common migraine types. Clinical relevance: This study highlights potential shared genetic mechanisms in migraine and ataxia disorders.