title: A novel mitochondrial MTND5 frameshift mutation causing isolated complex I deficiency, renal failure and myopathy.
abstract: Isolated complex I deficiency is the most commonly reported enzyme defect in paediatric mitochondrial disorders, and may arise due to mutations in nuclear-encoded structural or assembly genes, or the mitochondrial genome. We present the clinical, biochemical and molecular genetic data in a young girl whose clinical picture is dominated by chronic renal failure, myopathy and persistent lactic acidosis. An isolated complex I deficiency in muscle was identified due to a novel mutation (m.12425delA) in the MTND5 gene. This single nucleotide deletion is heteroplasmic and detectable in several tissues from the proband but not her mother, suggesting a de novo mutation event. The description of the first frameshift mutation in a mitochondrial complex I gene affirms mitochondrial DNA mutations as an important cause of isolated complex I deficiency in children and the importance of whole mitochondrial genome sequencing in the diagnostic work-up to elucidate the underlying molecular genetic abnormality and provide important genetic advice.
authors.affiliation: Mitochondrial Research Group and NCG Rare Mitochondrial Disorders of Adults and Children Service, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Charlotte L
authors.initials: CL
authors.lastname: Alston
authors.forename: Monika
authors.initials: M
authors.lastname: Morak
authors.forename: Christopher
authors.initials: C
authors.lastname: Reid
authors.forename: Iain P
authors.initials: IP
authors.lastname: Hargreaves
authors.forename: Simon A S
authors.initials: SA
authors.lastname: Pope
authors.forename: John M
authors.initials: JM
authors.lastname: Land
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Heales
authors.forename: Rita
authors.initials: R
authors.lastname: Horvath
authors.forename: Helen
authors.initials: H
authors.lastname: Mundy
authors.forename: Robert W
authors.initials: RW
authors.lastname: Taylor
mesh_terms: D000140:Acidosis, Lactic / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D002648:Child; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics; D042967:Electron Transport Complex I / Q000172:deficiency* / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics; D017353:Gene Deletion; D005838:Genotype; D006801:Humans; D028361:Mitochondrial Diseases / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D024101:Mitochondrial Proteins / Q000235:genetics*; D009135:Muscular Diseases / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D051437:Renal Insufficiency / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology
chemical_list: D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; C481838:MT-ND5 protein, human; D042967:Electron Transport Complex I