CACNA1A mutations

In 1996, Ophoff et al.1 showed that familial hemiplegic migraine (FHM) and episodic ataxia type 2 (EA2) are both caused by mutations within CACNA1A, a gene encoding for the α1A subunit of a neuronal P/Q type calcium channel. Molecular analysis of five unrelated FHM and two EA2 families as well as one EA2 sporadic case suggested that these two clinically distinct conditions may be due to distinct types of mutations within CACNA1A: missense mutations in FHM and truncating mutations in EA2.1,2 More recently, a recurrent missense mutation, T666M, was identified in most families affected by FHM with progressive cerebellar ataxia.3 In this issue, Battistini et al.4 and Carrera et al.5 identified in two additional FHM families missense mutations located within important functional regions of CACNA1A. Also in this issue, Jen et al.6 identify a truncating mutation within an EA2 family. Interestingly, two members of the pedigree experienced hemiparesis during some of their ataxic spells. Altogether these data confirmed the distinct nature of the mutations causing these two conditions. However, the detailed clinical analyses of the families reported in this issue of Neurology bring additional clinically important information.