A Novel Mutation in MARS in a Patient with Charcot-Marie-Tooth Disease, Axonal, Type 2U with Congenital Onset
| Autor: | Meredith K. Gillespie, Hugh J. McMillan, Izabella A. Pena, Kym M. Boycott, Kristin D. Kernohan, Rebecca Meyer-Schuman, Anthony Antonellis |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Neuromuscular disease Case Report Methionine-tRNA Ligase Disease Biology 03 medical and health sciences 0302 clinical medicine Charcot-Marie-Tooth Disease Charcot-Marie-Tooth disease type 2U medicine Humans Child Gene Exome sequencing Genetics Genetic heterogeneity CMT2U MARS medicine.disease Phenotype Protein Structure Tertiary 3. Good health Congenital onset 030104 developmental biology Neurology Mutation early-onset neuropathy Female Neurology (clinical) exome sequencing Novel mutation 030217 neurology & neurosurgery |
| Zdroj: | Journal of Neuromuscular Diseases |
| ISSN: | 2214-3602 2214-3599 |
| DOI: | 10.3233/jnd-190404 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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