Descrição
Background: Different mutations in the 1A-subunit of
the brain P/Q-type calcium channel gene (CACNA1A) are
responsible for familial hemiplegic migraine (FHM), episodic
ataxia type 2, and spinocerebellar ataxia type 6
(SCA6). Missense and splice site mutations have been
found in FHM and episodic ataxia type 2, respectively,
whereas a CAG repeat in the CACNA1A gene was found
expanded in patients with SCA6.
Objective: To identify the disease causing mutation in
a large family of patients with phenotypes of hemiplegic
migraine with or without cerebellar signs or permanent
cerebellar ataxia without migraine inherited in a dominant
manner.
Patients and Methods: We examined 15 patients
from a large family identified through a systematic survey
of hereditary ataxias being conducted in Portugal.
Linkage analysis was performed with CACNA1A gene
markers, and mutation analysis was performed by single strand conformational polymorphism analysis
and sequencing.
Results: Genetic linkage analysis with CACNA1A intragenic markers showed positive LOD scores. The maximal LOD score was obtained with the polymorphic CAG repeat (Zmax=4.47, =0). By single-strand conformational polymorphism analysis, a shift in exon 13 of the CACNA1A gene was detected in all patients.AG-to-A substitution was then identified, resulting in an arginine-to-glutamine change at codon 583 of this calcium channel 1A-subunit.
Conclusions: The disease-causing mutation in this family was identified, showing that a unique mutation in the CACNA1A gene causes several phenotypes, including those of SCA6 and FHM, thus suggesting that SCA6 and FHM are not only allelic diseases but are the same disorder with a large phenotypic variability.
; Barros, J. 
