Molecular exploration of patients suffering from Episodic Type 2 ataxia without any punctual mutation identified in CACNA1A: search for major rearrangements.
Starting date: January 2007
Investigator-Coordinator: Dr. F.Riant – Molecular Genetics Department – Lariboisière Hospital – Paris.
Rationale: Episodic Type 2 ataxia (EA2) is an autosomal dominant paroxysmal cerebellar ataxia caused by mutations in the CACNA1A gene (chromosome 19p13) which encodes for a calcium channel. The search for mutations in this gene can be carried out during molecular diagnosis and the approach used until now by the various teams has been screening for exons by SSCP or sequencing. This approach has revealed punctual mutations, most of which lead to the appearance of a premature stop codon. However, in a far from negligible number of cases, no mutation has been revealed using these techniques. Because of the nature of the mutations most commonly identified in this disease, the stop mutations, we have put forward the hypothesis of major rearrangements in the CACNA1A gene that are not detectable using conventional screening techniques.
Objective: The aim of this study is to seek the major deletions in the CACNA1A gene in people with EA2.
Selection, inclusion of patients and carrying out of the study: Some forty patients will be included in this study. They will have clinical signs suggestive of EA2 but no mutations revealed by conventional screening techniques (sequencing and/or SSCP). The search for deletions will be carried out using the QMPSF technique (Quantitative Multiplex PCR or Short Fluorescent fragments).
Expected results: The aim of the study is to determine the spectrum and frequency of these mutations to assess whether it is worthwhile systematically screening for them when dealing with an application for molecular diagnosis of this disease.