SLC25A46 Mutations Associated with Autosomal Recessive Cerebellar Ataxia in North African Families
| Autor: | 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, Sampath Arepalli |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
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 |
| Zdroj: | Neuro-degenerative diseases. 17(4-5) |
| ISSN: | 1660-2862 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|