title: A novel mitochondrial ATP8 gene mutation in a patient with apical hypertrophic cardiomyopathy and neuropathy.
abstract: To identify the biochemical and molecular genetic defect in a 16-year-old patient presenting with apical hypertrophic cardiomyopathy and neuropathy suspected for a mitochondrial disorder.Measurement of the mitochondrial energy-generating system (MEGS) capacity in muscle and enzyme analysis in muscle and fibroblasts were performed. Relevant parts of the mitochondrial DNA were analysed by sequencing.A homoplasmic nonsense mutation m.8529G→A (p.Trp55X) was found in the mitochondrial ATP8 gene in the patient's fibroblasts and muscle tissue. Reduced complex V activity was measured in the patient's fibroblasts and muscle tissue, and was confirmed in cybrid clones containing patient-derived mitochondrial DNAWe describe the first pathogenic mutation in the mitochondrial ATP8 gene, resulting in an improper assembly and reduced activity of the complex V holoenzyme.
authors.affiliation: Geert Grooteplein 10 PO Box 9101, 6500 HB Nijmegen, Netherlands.
authors.forename: An I
authors.initials: AI
authors.lastname: Jonckheere
authors.forename: Marije
authors.initials: M
authors.lastname: Hogeveen
authors.forename: Leo
authors.initials: L
authors.lastname: Nijtmans
authors.forename: Mariel
authors.initials: M
authors.lastname: van den Brand
authors.forename: Antoon
authors.initials: A
authors.lastname: Janssen
authors.forename: Heleen
authors.initials: H
authors.lastname: Diepstra
authors.forename: Frans
authors.initials: F
authors.lastname: van den Brandt
authors.forename: Bert
authors.initials: B
authors.lastname: van den Heuvel
authors.forename: Frans
authors.initials: F
authors.lastname: Hol
authors.forename: Tom
authors.initials: T
authors.lastname: Hofste
authors.forename: Livia
authors.initials: L
authors.lastname: Kapusta
authors.forename: U
authors.initials: U
authors.lastname: Dillmann
authors.forename: M
authors.initials: M
authors.lastname: Shamdeen
authors.forename: J
authors.initials: J
authors.lastname: Smeitink
authors.forename: J
authors.initials: J
authors.lastname: Smeitink
authors.forename: Richard
authors.initials: R
authors.lastname: Rodenburg