1. SLC25A46 Mutations Associated with Autosomal Recessive Cerebellar Ataxia in North African Families
- Author
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Alexandra Durr, Monia B. Hammer, Rim Amouri, Ghada Eleuch-Fayache, Sean B. Chong, Jinhui Ding, Steven J. Clipman, Andrew B. Singleton, Fanny Mochel, Perrine Charles, Houda Nehdi, Giovanni Stevanin, Marie Coutelier, Dena G. Hernandez, Elisa Majounie, J. Raphael Gibbs, Alexis Brice, Fayçal Hentati, Yosr Bouhlal, and Sampath Arepalli
- Subjects
0301 basic medicine ,Adult ,Male ,genetic structures ,Cerebellar Ataxia ,DNA Mutational Analysis ,Biology ,Article ,Mitochondrial Proteins ,03 medical and health sciences ,Consanguinity ,0302 clinical medicine ,medicine ,Humans ,Phosphate Transport Proteins ,Genetics ,Family Health ,Genetic heterogeneity ,Autosomal recessive cerebellar ataxia ,medicine.disease ,Magnetic Resonance Imaging ,eye diseases ,030104 developmental biology ,Neurology ,Mutation ,North America ,North african ,Female ,sense organs ,Neurology (clinical) ,human activities ,030217 neurology & neurosurgery - Abstract
Background: Autosomal recessive cerebellar ataxias (ARCA) are a complex group of neurodegenerative disorders with high clinical and genetic heterogeneity. In most cases, the cerebellar ataxia is not pure, and complicating clinical features such as pyramidal signs or extraneurological features are found. Objective: To identify the genetic origin of the cerebellar ataxia for 3 consanguineous North African families presenting with ARCA. Methods: Genome-wide high-density SNP genotyping and whole-exome sequencing were performed followed by Sanger sequencing for mutation confirmation. Results: Two variants were identified in SLC25A46. Mutations in this gene have been previously associated with Charcot-Marie-Tooth type 2 and optic atrophy. While the previously reported variant p.Arg340Cys seems to be consistently associated with the same clinical features such as childhood onset, optic atrophy, gait and speech difficulties, and wasting of the lower limbs, the patient with the novel mutation p.Trp160Ser did not present with optic atrophy and his ocular abnormalities were limited to nystagmus and saccadic pursuit. Conclusion: In this study, we report a novel variant (p.Trp160Ser) in SLC25A46 and we broaden the phenotypic spectrum associated with mutations in SLC25A46.
- Published
- 2016