A deletion in the human QP-C gene causes a complex III deficiency resulting in hypoglycaemia and lactic acidosis

被引:108
作者
Haut, S
Brivet, M
Touati, G
Rustin, P
Lebon, S
Garcia-Cazorla, A
Saudubray, JM
Boutron, A
Legrand, A
Slama, A
机构
[1] Hop Bicetre, AP HP, Lab Biochim 1, F-94275 Le Kremlin Bicetre, France
[2] Hop Necker Enfants Malad, Serv Pediat, F-5743 Paris, France
[3] Hop Necker Enfants Malad, INSERM, U393, Unite Rech Handicaps Genet Enfant, F-5743 Paris, France
关键词
D O I
10.1007/s00439-003-0946-0
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Mitochondrial respiratory chain complex III (ubiquinol-cytochrome c reductase) consists of 11 subunits, only one (cytochrome b) being encoded by the mitochondrial DNA. Disorders of complex III are comparatively rare but are nevertheless present as a clinically heterogeneous group of diseases. To date, no mutation in any of the nuclear-encoded subunits has been described. We report here a deletion in the nuclear gene UQCRB encoding the human ubiquinone-binding protein of complex III (QP-C subunit or subunit VII) in a consanguineous family with an isolated complex III defect. In the proband, a homozygous 4-bp deletion was identified at nucleotides 338-341 of the cDNA predicting both a change in the last seven amino acids and an addition of a stretch of 14 amino acids at the C-terminal end of the protein. Both parents were found to be heterozygous for the deletion, which was absent from 55 controls. Low temperature (-196degreesC) spectral studies performed on isolated mitochondria from cultured skin fibroblast of the proband showed a decreased cytochrome b content suggestive of a role for the QP-C subunit in the assembly or maintenance of complex III structure.
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页码:118 / 122
页数:5
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