title: Mitochondrial complex III deficiency associated with a homozygous mutation in UQCRQ.
abstract: A consanguineous Israeli Bedouin kindred presented with an autosomal-recessive nonlethal phenotype of severe psychomotor retardation and extrapyramidal signs, dystonia, athetosis and ataxia, mild axial hypotonia, and marked global dementia with defects in verbal and expressive communication skills. Metabolic workup was normal except for mildly elevated blood lactate levels. Brain magnetic resonance imaging (MRI) showed increased density in the putamen, with decreased density and size of the caudate and lentiform nuclei. Reduced activity specifically of mitochondrial complex III and variable decrease in complex I activity were evident in muscle biopsies. Homozygosity of affected individuals to UQCRB and to BCSIL, previously associated with isolated complex III deficiency, was ruled out. Genome-wide linkage analysis identified a homozygosity locus of approximately 9 cM on chromosome 5q31 that was further narrowed down to 2.14 cM, harboring 30 genes (logarithm of the odds [LOD] score 8.82 at theta = 0). All 30 genes were sequenced, revealing a single missense (p.Ser45Phe) mutation in UQCRQ (encoding ubiquinol-cytochrome c reductase, complex III subunit VII, 9.5 kDa), one of the ten nuclear genes encoding proteins of mitochondrial complex III.
authors.affiliation: The Morris Kahn Laboratory of Human Genetics, National Institute for Biotechnology in the Negev, Faculty of Health Sciences, Ben-Gurion University, Beer-Sheva 84105, Israel.
authors.forename: Ortal
authors.initials: O
authors.lastname: Barel
authors.forename: Zamir
authors.initials: Z
authors.lastname: Shorer
authors.forename: Hagit
authors.initials: H
authors.lastname: Flusser
authors.forename: Rivka
authors.initials: R
authors.lastname: Ofir
authors.forename: Ginat
authors.initials: G
authors.lastname: Narkis
authors.forename: Gal
authors.initials: G
authors.lastname: Finer
authors.forename: Hanah
authors.initials: H
authors.lastname: Shalev
authors.forename: Ahmad
authors.initials: A
authors.lastname: Nasasra
authors.forename: Ann
authors.initials: A
authors.lastname: Saada
authors.forename: Ohad S
authors.initials: OS
authors.lastname: Birk
mesh_terms: D002675:Child, Preschool; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D003241:Consanguinity; D014450:Electron Transport Complex III / Q000172:deficiency* / Q000235:genetics*; D008040:Genetic Linkage; D015894:Genome, Human; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D009154:Mutation; D010375:Pedigree
chemical_list: D014450:Electron Transport Complex III