The first biallelic missense mutation in the FXN gene in a consanguineous Turkish family with Charcot-Marie-Tooth-like phenotype
| Autor: | Yesim Parman, Arman Çakar, Gulshan Yunisova, Ayse Candayan, A. Nazli Basak, Esra Battaloglu, Hacer Durmus |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Adult Male congenital hereditary and neonatal diseases and abnormalities Ataxia Adolescent Turkey Mutation Missense Biology Compound heterozygosity 03 medical and health sciences Cellular and Molecular Neuroscience Young Adult 0302 clinical medicine Charcot-Marie-Tooth Disease Iron-Binding Proteins Genetics medicine Missense mutation Humans Family Gene Genetics (clinical) Homozygote Human genetics nervous system diseases Pedigree 030104 developmental biology Phenotype Mutation (genetic algorithm) Frataxin biology.protein Female medicine.symptom Trinucleotide repeat expansion 030217 neurology & neurosurgery |
| Zdroj: | Neurogenetics. 21(1) |
| ISSN: | 1364-6753 |
| Popis: | Charcot-Marie-Tooth (CMT) disease is the most common inherited neuropathy with a prevalence of 1 in 2500 individuals worldwide. Here, we report three Turkish siblings from consanguineous parents presenting with a CMT-like phenotype who carry a homozygous c.493C>T, p.Arg165Cys mutation in the FXN gene that is the only known causative gene for Friedreich's ataxia (FRDA). The identified missense mutation has been reported previously in two FRDA cases in compound heterozygosity with the common GAA repeat expansion in the first intron of the FXN gene. Analysis of skin biopsy samples from our family indicated that the mutation does not affect the expression levels of the frataxin, pointing to functional impairment of the corresponding protein. The CMT phenotype in the siblings was associated with visual impairment, optic nerve atrophy, and dysarthria. To the best of our knowledge, this family represents the first FXN missense mutation in homozygosity and challenges the notion that missense mutations have not been reported yet due to their embryonic lethality. Furthermore, this finding poses an interesting genetic overlap between autosomal recessive CMT and FRDA that we believe may have important implications on understanding the pathogenesis of these neurological disorders. |
| Databáze: | OpenAIRE |
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