Missense mutations of CACNA1A are a frequent cause of autosomal dominant nonprogressive congenital ataxia

background: mutations in the CACNA1A gene, encoding the pore-forming CaV2.1 (P/Qtype) channel al. a subunit, localized at presynaptic terminals of brain and cerebellar neurons, result in clinically variable neurological disorders including hemiplegic migraine (HM) and episodic or progressive adult-onset ataxia (EA2, SCA6). most recently, CACNAIA mutations have been identified in patients with nonprogressive congenital ataxia (NPCA). methods: we performed targeted resequencing of known genes involved in cerebellar dysfunction, in 48 patients with congenital or early onset ataxia associated with cerebellar and/or vermis atrophy. results: de novo missense mutations of CACNAIA were found in four patients (4/48,-8.3%). three of them developed migraine before or after the onset of ataxia. seizures were present in half of the cases. conclusion: our results expand the clinical and mutational spectrum of CACNA1A-related phenotype in childhood and suggest that CACNA1A screening should be implemented in this subgroup of ataxias.