Episodic ataxia type 2. Three novel truncating mutations and one novel missense mutation in the CACNA1A gene

van den Maagdenberg, AMJM; Kors, EE; Brunt, ER; Van Paesschen, Wim; Pascual, J; Ravine, D; Keeling, S; Vanmolkot, KRJ; Vermeulen, FLMG; Terwindt, GM; Haan, J; Frants, RR; Ferrari, MD

doi:10.1007/s00415-002-0860-8

Episodic ataxia type 2. Three novel truncating mutations and one novel missense mutation in the CACNA1A gene

Author:

van den Maagdenberg, AMJM

Kors, EE ; Brunt, ER ; Van Paesschen, Wim ; Pascual, J ; Ravine, D ; Keeling, S ; Vanmolkot, KRJ ; Vermeulen, FLMG ; Terwindt, GM ; Haan, J ; Frants, RR ; Ferrari, MD

Keywords:

Adult, Amino Acid Sequence, Calcium Channels, Calcium Channels, P-Type, Cerebellum, Chromosome Mapping, Chromosomes, Human, Pair 19, DNA Mutational Analysis, Exons, Female, Genetic Screening, Histidine, Humans, Male, Middle Aged, Mutation, Missense, Pedigree, Protein Structure, Tertiary, Spinocerebellar Degenerations, Trinucleotide Repeat Expansion, Science & Technology, Life Sciences & Biomedicine, Clinical Neurology, Neurosciences & Neurology, episodic ataxia type 2, EA-2, CACNA1A, calcium channel, mutation analysis, CEREBELLAR-ATAXIA, CALCIUM-CHANNEL, CHROMOSOME 19P, MAPS, REGION, Genetic Testing, 1103 Clinical Sciences, 1109 Neurosciences, Neurology & Neurosurgery, 3202 Clinical sciences, 3209 Neurosciences

Abstract:

We analysed the CACNA1A gene, located on chromosome 19p13, in three unrelated families and one sporadic case with episodic ataxia type 2 (EA-2). In two of the families and the sporadic patient, novel truncating mutations, which disrupt the reading frame and result in a premature stop of the CACNA1A protein, were identified in exons 14, 16 and 26. In the remaining family, a novel missense mutation (H253Y) was found. Of the twenty two EA-2 mutations identified thus far, including those of the present study, seventeen are truncating mutations and five are missense mutations, all resulting in an EA-2 clinical phenotype.