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.