title: Identification and functional characterization of a novel MTFMT mutation associated with selective vulnerability of the visual pathway and a mild neurological phenotype.
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.
authors.affiliation: Laboratory of Neurogenetics of Motion, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada.|Department of Neuroradiology, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada.
authors.forename: Roberta
authors.initials: R
authors.lastname: La Piana
authors.affiliation: Department of Human Genetics, Montreal Neurological Institute, McGill University, Montreal, QC, Canada.|Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Woranontee
authors.initials: W
authors.lastname: Weraarpachai
authors.affiliation: Department of Ophthalmology, Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal, Montreal, QC, Canada.
authors.forename: Luis H
authors.initials: LH
authors.lastname: Ospina
authors.affiliation: Department of Human Genetics, McGill University, Genome Québec Innovation Center, Montreal, QC, Canada.
authors.forename: Martine
authors.initials: M
authors.lastname: Tetreault
authors.affiliation: Department of Human Genetics, McGill University, Genome Québec Innovation Center, Montreal, QC, Canada.
authors.forename: Jacek
authors.initials: J
authors.lastname: Majewski
authors.affiliation: Departments of Radiology and Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
authors.forename: G
authors.initials: G
authors.lastname: Bruce Pike
authors.affiliation: Department of Radiology, Radiotherapy and Nuclear Medicine, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Decarie
authors.affiliation: Department of Neuroradiology, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada.
authors.forename: Donatella
authors.initials: D
authors.lastname: Tampieri
authors.affiliation: Laboratory of Neurogenetics of Motion, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada.|Department of Human Genetics, Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
authors.forename: Bernard
authors.initials: B
authors.lastname: Brais
authors.affiliation: Department of Human Genetics, Montreal Neurological Institute, McGill University, Montreal, QC, Canada. eric@ericpc.mni.mcgill.ca.|Montreal Neurological Institute, 3801 University Street, Montreal, QC, H3A 2B4, Canada. eric@ericpc.mni.mcgill.ca.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Shoubridge
mesh_terms: D060825:Cognitive Dysfunction / Q000150:complications / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D019877:Hydroxymethyl and Formyl Transferases / Q000235:genetics*; D028361:Mitochondrial Diseases / Q000150:complications / Q000235:genetics*; D010641:Phenotype; D014786:Vision Disorders / Q000235:genetics*; D014795:Visual Pathways / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
chemical_list: D019877:Hydroxymethyl and Formyl Transferases; C021561:methionyl-tRNA formyltransferase
keywords: Leukoencephalopathy; MTFMT; OXPHOS defects; Optic pathway; Whole exome sequencing