Mitochondrial Complex III Deficiency Associated with a Homozygous Mutation in UQCRQ

Ortal Barel, Zamir Shorer, Hagit Flusser, Rivka Ofir, Ginat Narkis, Gal Finer, Hanah Shalev, Ahmad Nasasra, Ann Saada, Ohad S. Birk*

*Corresponding author for this work

Research output: Contribution to journalArticle

67 Scopus citations

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 θ = 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.

Original languageEnglish (US)
Pages (from-to)1211-1216
Number of pages6
JournalAmerican journal of human genetics
Volume82
Issue number5
DOIs
StatePublished - May 9 2008

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Barel, O., Shorer, Z., Flusser, H., Ofir, R., Narkis, G., Finer, G., Shalev, H., Nasasra, A., Saada, A., & Birk, O. S. (2008). Mitochondrial Complex III Deficiency Associated with a Homozygous Mutation in UQCRQ. American journal of human genetics, 82(5), 1211-1216. https://doi.org/10.1016/j.ajhg.2008.03.020