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Florence Riant, MD; Reda Mourtada, MD; Pascale Saugier-Veber, MD; Elisabeth Tournier-Lasserve, MD

Arch Neurol. 2008;65(6):817-820.

Background  Episodic ataxia (EA) is an ion channel disorder that manifests as paroxysmal attacks of imbalance and incoordination. Episodic ataxia type 2 (EA2) is characterized by prolonged episodes of ataxia with interictal nystagmus and is caused by mutations in CACNA1A. All mutations identified thus far (to our knowledge) are nonsense or missense point mutations.

Objective  To describe a family with EA2 having a novel mutation deleting several exons of CACNA1A.

Design  Clinical and molecular study of a family manifesting EA2 attacks.

Setting  Academic research.

Patients  DNA was extracted from blood samples of 3 family members.

Main Outcome Measures  Microsatellite genotyping of CACNA1A, quantitative multiplex polymerase chain reaction of short fluorescent fragments (QMPSF), and sequencing were performed.

Results  Genotyping of CACNA1A showed nonmendelian inheritance of a CAG repeat located at the 3' end of the gene in a mother and daughter, suggesting a deletion event, which was subsequently confirmed by QMPSF analysis and sequencing. This 39.5-kilobase deletion removes the last 16 coding exons of the gene.

Conclusion  Deletion of several exons of CACNA1A may cause EA2 and should be assessed in patients having EA2 without a CACNA1A point mutation.

Author Affiliations: Laboratoire de Génétique, Groupe Hospitalier Lariboisière–Fernand Widal, Groupement Hospitalier–Universitaire Nord, Assistance Publique–Hôpitaux de Paris, and Site Lariboisière, Faculté de Médecine, Institut National de la Santé et de la Récherche Médicale (INSERM) Unité 740 (Drs Riant and Tournier-Lasserve), and Site Lariboisière, Faculté de Médecine, Université Paris 7–Denis Diderot (Dr Tournier-Lasserve), Paris; Neurology Department, Pontchaillou Hospital, Rennes (Dr Mourtada); and Genetics Department, Rouen University Hospital, and Institute for Biomedical Research, University of Rouen, INSERM Unité 614, Rouen (Dr Saugier-Veber); France.

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