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A Novel Mutation in MARS in a Patient with Charcot-Marie-Tooth Disease, Axonal, Type 2U with Congenital Onset
Charcot-Marie-Tooth disease is a phenotypically and genetically heterogeneous group of disorders affecting both motor and sensory neurons. Exome sequencing has driven discovery of genes responsible for Charcot-Marie-Tooth disease with more than 70 genes now associated with this neuromuscular disease...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
IOS Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889022/ https://www.ncbi.nlm.nih.gov/pubmed/31356216 http://dx.doi.org/10.3233/JND-190404 |
Sumario: | Charcot-Marie-Tooth disease is a phenotypically and genetically heterogeneous group of disorders affecting both motor and sensory neurons. Exome sequencing has driven discovery of genes responsible for Charcot-Marie-Tooth disease with more than 70 genes now associated with this neuromuscular disease. The MARS gene was recently reported as the cause of Charcot-Marie-Tooth 2U, a slowly progressive axonal sensorimotor polyneuropathy with adult-onset reported in six patients. We report here a patient with a progressive, early childhood-onset, motor-predominant form of Charcot-Marie-Tooth disease. Exome sequencing identified a novel MARS variant (c.1189G>A; p.Ala397Thr) that was not present in her unaffected mother; her unaffected father was unavailable. Further studies using structural modeling and a yeast humanization assay support pathogenicity of the variant. Our study expands the phenotype of Charcot-Marie-Tooth 2U, while highlighting the utility of functional assays to evaluate variant pathogenicity. |
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