Identification of novel and recurrent CACNA1A gene mutations in fifteen patients with episodic ataxia type 2

Elide Mantuano, Silvia Romano, Liana Veneziano, Cinzia Gellera, Barbara Castellotti, Sara Caimi, Daniela Testa, Margherita Estienne, Giovanna Zorzi, Marianna Bugiani, Yusuf A. Rajabally, Maria J Garcìa Barcina, Serena Servidei, Aurora Panico, Marina Frontali, Caterina Mariotti

Research output: Contribution to journalArticlepeer-review


Episodic ataxia type 2 is a rare autosomal dominant disease characterized by recurrent attacks of vertigo and cerebellar ataxia. The disease was caused by mutations in the CACNA1A gene, on chromosome 19p. We perform a mutational screening in a group of 43 unrelated patients. Forty-two patients presented episodes of disequilibrium and ataxia, and one child was studied because of the occurrence of episodic torticollis. The genetic analysis showed 15 mutated patients (35%). In 13 cases we found novel CACNA1A gene mutations, including missense, protein truncating, and aberrant splicing mutations. Two truncating mutations lead to the uppermost premature stop so far reported, challenging recent hypotheses on dominant negative effect. In patients without CACNA1A mutations, molecular testing for CACNB4 gene mutations excluded this genetic subtype. Clinical features of mutated subjects mostly confirmed previous sign and symptoms associated with EA2, including paroxysmal torticollis and mental retardation. CACNA1A mutated patients have an earlier age at onset, interictal nystagmus, and abnormalities of ocular movements. A review of all CACNA1A mutations so far reported showed that they are mainly located downstream exon 18. Our data substantially increase the number of the described CACNA1A mutations, and propose clinical and molecular criteria for a more focused genetic screening.

Original languageEnglish
Pages (from-to)30-36
Number of pages7
JournalJournal of the Neurological Sciences
Issue number1-2
Publication statusPublished - Apr 15 2010


  • Acetazolamide
  • Calcium channel
  • EA2
  • Episodic ataxia
  • Paroxysmal torticollis

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology


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