title: Unusual clinical presentations in four cases of Leigh disease, cytochrome C oxidase deficiency, and SURF1 gene mutations.
abstract: Mutations in the SURF1 gene are the most frequent causes of Leigh disease with cytochrome c oxidase deficiency. We describe four children with novel SURF1 mutations and unusual features: three had prominent renal symptoms and one had ragged red fibers in the muscle biopsy. We identified five pathogenic mutations in SURF1: two mutations were novel, an in-frame nonsense mutation (834G-->A) and an out-of-frame duplication (820-824dupTACAT). Although renal manifestations have not been described in association with SURF1 mutations, they can be part of the clinical presentation. Likewise, mitochondrial proliferation in muscle (with ragged red fibers) is most unusual in Leigh disease but might be part of an emerging phenotype.
authors.affiliation: Department of Neurology, Columbia University, New York, NY, USA.
authors.forename: Stacey K H
authors.initials: SK
authors.lastname: Tay
authors.forename: Sabrina
authors.initials: S
authors.lastname: Sacconi
authors.forename: H Ohran
authors.initials: HO
authors.lastname: Akman
authors.forename: Judith F
authors.initials: JF
authors.lastname: Morales
authors.forename: Augusto
authors.initials: A
authors.lastname: Morales
authors.forename: Darryl C
authors.initials: DC
authors.lastname: De Vivo
authors.forename: Sara
authors.initials: S
authors.lastname: Shanske
authors.forename: Eduardo
authors.initials: E
authors.lastname: Bonilla
authors.forename: Salvatore
authors.initials: S
authors.lastname: DiMauro
mesh_terms: D030401:Cytochrome-c Oxidase Deficiency / Q000150:complications* / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007674:Kidney Diseases / Q000209:etiology; D007888:Leigh Disease / Q000150:complications* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D018482:Muscle, Skeletal / Q000473:pathology; D010641:Phenotype; D011506:Proteins / Q000235:genetics*
chemical_list: D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; C092928:Surf-1 protein