A NovelGBA2Gene Missense Mutation in Spastic Ataxia
doi: 10.1111/ahg.12045
pmid: 24252062
A NovelGBA2Gene Missense Mutation in Spastic Ataxia
Autosomal recessive cerebellar ataxias (ARCA) encompass a heterogeneous group of rare diseases that affect the cerebellum, the spinocerebellar tract and/or the sensory tracts of the spinal cord. We investigated a consanguineous Cypriot family with spastic ataxia, aiming towards identification of the causative mutation. Family members were clinically evaluated and studied at the genetic level. Linkage analysis at marker loci spanning known ARCA genes/loci revealed linkage to the APTX locus. Thorough investigation of the APTX gene excluded any possible mutation. Whole genome linkage screening using microsatellite markers and whole genome SNP homozygosity mapping using the Affymetrix Genome-Wide Human SNP Array 6.0 enabled mapping of the disease gene/mutation in this family to Chromosome 9p21.1-p13.2. Due to the large number of candidate genes within this region, whole-exome sequencing of the proband was performed and further analysis of the obtained data focused on the mapped interval. Further investigation of the candidate variants resulted in the identification of a novel missense mutation in the GBA2 gene. GBA2 mutations have recently been associated with hereditary spastic paraplegia and ARCA with spasticity. We hereby report a novel GBA2 mutation associated with spastic ataxia and suggest that GBA2 mutations may be a relatively frequent cause of ARCA.
- Imperial College London United Kingdom
- THE CYPRUS FOUNDATION FOR MUSCULAR DYSTROPHY RESEARCH Cyprus
- Cyprus Institute of Neurology and Genetics Cyprus
Genetic Markers, Male, Adolescent, Cerebellar Ataxia, Genotype, Genetic Linkage, Mutation, Missense, Genes, Recessive, Consanguinity, Intellectual Disability, Humans, Age of Onset, Chromosome Mapping, Optic Atrophy, Genetic Loci, Muscle Spasticity, Glucosylceramidase, Female, Genome-Wide Association Study, Microsatellite Repeats
Genetic Markers, Male, Adolescent, Cerebellar Ataxia, Genotype, Genetic Linkage, Mutation, Missense, Genes, Recessive, Consanguinity, Intellectual Disability, Humans, Age of Onset, Chromosome Mapping, Optic Atrophy, Genetic Loci, Muscle Spasticity, Glucosylceramidase, Female, Genome-Wide Association Study, Microsatellite Repeats
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