title: Mutations in mitochondrial complex I assembly factor NDUFAF3 cause Leigh syndrome.
abstract: NDUFAF3 is an assembly factor of mitochondrial respiratory chain complex I. Variants in NDUFAF3 have been identified as a cause of severe multisystem mitochondrial disease. In a patient presenting with Leigh syndrome, which has hitherto not been described as a clinical feature of NDUFAF3 deficiency, we identified a novel homozygous variant and confirmed its pathogenicity in patient fibroblasts studies. Furthermore, we present an analysis of complex I assembly routes representative of each functional module and, thereby, link NDUFAF3 to a specific step in complex I assembly. Therefore, our report expands the phenotype of NDUFAF3 deficiency and further characterizes the role of NDUFAF3 in complex I biogenesis.
authors.affiliation: Department of Pediatrics, Radboud Centre for Mitochondrial Medicine, Radboud University Medical Centre, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, The Netherlands; Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Children's Hospital Duesseldorf, Heinrich Heine University, Moorenstr. 5, 40225 Düsseldorf, Germany. Electronic address: Fabian.Baertling@med.uni-duesseldorf.de.
authors.forename: Fabian
authors.initials: F
authors.lastname: Baertling
authors.affiliation: Department of Pediatrics, Radboud Centre for Mitochondrial Medicine, Radboud University Medical Centre, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, The Netherlands.
authors.forename: Laura
authors.initials: L
authors.lastname: Sánchez-Caballero
authors.affiliation: Department of Pediatrics, Radboud Centre for Mitochondrial Medicine, Radboud University Medical Centre, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, The Netherlands.
authors.forename: Sharita
authors.initials: S
authors.lastname: Timal
authors.affiliation: Department of Pediatrics, Radboud Centre for Mitochondrial Medicine, Radboud University Medical Centre, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, The Netherlands.
authors.forename: Mariël Am
authors.initials: MA
authors.lastname: van den Brand
authors.affiliation: Kuala Lumpur Hospital, Jalan Pahang, 50586 Kuala Lumpur, Malaysia.
authors.forename: Lock Hock
authors.initials: LH
authors.lastname: Ngu
authors.affiliation: Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Children's Hospital Duesseldorf, Heinrich Heine University, Moorenstr. 5, 40225 Düsseldorf, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Distelmaier
authors.affiliation: Department of Pediatrics, Radboud Centre for Mitochondrial Medicine, Radboud University Medical Centre, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, The Netherlands.
authors.forename: Richard Jt
authors.initials: RJ
authors.lastname: Rodenburg
authors.affiliation: Department of Pediatrics, Radboud Centre for Mitochondrial Medicine, Radboud University Medical Centre, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, The Netherlands.
authors.forename: Leo Gj
authors.initials: LG
authors.lastname: Nijtmans
mesh_terms: D002478:Cells, Cultured; D059472:Exome; D017809:Fatal Outcome; D005260:Female; D005347:Fibroblasts / Q000166:cytology; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D007223:Infant; D007888:Leigh Disease / Q000235:genetics* / Q000473:pathology; D024101:Mitochondrial Proteins / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D017422:Sequence Analysis, DNA / Q000379:methods*
chemical_list: D024101:Mitochondrial Proteins; C541710:NDUFAF3 protein, human
keywords: Assembly factor; Complex I; Leigh syndrome; NDUFAF3; OXPHOS