Clinical and molecular evidence of possible digenic inheritance for MFN2/GDAP1 genes in Charcot-Marie-Tooth disease
| Autor: | Renée Barreda Fierro, Camilo E. Villarroel Cortés, Juan Carlos Zenteno, Patricia Herrera Mora |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Genetics congenital hereditary and neonatal diseases and abnormalities MFN2 Sensory polyneuropathy Molecular evidence Biology Digenic inheritance Phenotype nervous system diseases 03 medical and health sciences Tooth disease 030104 developmental biology 0302 clinical medicine Neurology Pediatrics Perinatology and Child Health Genotype Neurology (clinical) Gene 030217 neurology & neurosurgery Genetics (clinical) |
| Zdroj: | Neuromuscular Disorders. 30:986-990 |
| ISSN: | 0960-8966 |
| Popis: | Charcot Marie Tooth disease (CMT) is a progressive motor and sensory polyneuropathy, it is characterized by a very heterogeneous molecular basis and phenotype. MFN2 and GDAP1 participate in mitochondrial energy metabolism and the rare coinheritance of its pathogenic variants has been associated with a cumulative effect in the observed phenotype. We describe a patient with a severe axonal CMT and inherited heterozygous MFN2 (p.Leu741Val) and GDAP1 (p.Gln163*) variants. In accordance with a possible digenic inheritance, none of the heterozygous carriers in his family were symptomatic or exhibited electrophysiological abnormalities. We also review all of the previously reported patients with coinheritance of variants in these two genes; similar to our patient, all exhibit a predominantly axonal severe CMT phenotype. Our findings expand the genotypic spectrum of CMT and further support that digenic inheritance should be considered for analyzing and counseling CMT patients. |
| Databáze: | OpenAIRE |
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