Identification and Functional Characterization of a Novel MTFMT Mutation Associated with Selective Vulnerability of the Visual Pathway and a Mild Neurological Phenotype

Overview

Journal Neurogenetics

Specialty Neurology

Date 2017 Jan 7

PMID 28058511

Citations 8

Authors

Roberta La Piana

Woranontee Weraarpachai

Luis H Ospina

Martine Tetreault

Jacek Majewski

G Bruce Pike

Jean-Claude Decarie

Donatella Tampieri

Bernard Brais

Eric A Shoubridge

Affiliations

Soon will be listed here.

Abstract

Mitochondrial protein synthesis is initiated by formylated tRNA-methionine, which requires the activity of MTFMT, a methionyl-tRNA formyltransferase. Mutations in MTFMT have been associated with Leigh syndrome, early-onset mitochondrial leukoencephalopathy, microcephaly, ataxia, and cardiomyopathy. We identified compound heterozygous MTFMT mutations in a patient with a mild neurological phenotype and late-onset progressive visual impairment. MRI studies documented a progressive and selective involvement of the retrochiasmatic visual pathway. MTFMT was undetectable by immunoblot analysis of patient fibroblasts, resulting in specific defects in mitochondrial protein synthesis and assembly of the oxidative phosphorylation complexes. This report expands the clinical and MRI phenotypes associated with MTFMT mutations, illustrating the complexity of genotype-phenotype relationships in mitochondrial translation disorders.

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