Mutations in CYC1, Encoding Cytochrome c1 Subunit of Respiratory Chain Complex III, Cause Insulin-Responsive Hyperglycemia

被引：52

作者：

Gaignard, Pauline ^{[1
]}

Menezes, Minal ^{[2
]}

Schiff, Manuel ^{[3
,4
,5
]}

Bayot, Aurelien ^{[3
,4
]}

Rak, Malgorzata ^{[3
,4
]}

de Baulny, Helene Ogler ^{[5
]}

Su, Chen-Hsien ^{[6
]}

Gilleron, Mylene ^{[7
,8
,9
]}

Lombes, Anne ^{[7
,8
,9
]}

Abida, Heni ^{[6
]}

Tzagoloff, Alexander ^{[6
]}

Riley, Lisa ^{[10
]}

Cooper, Sandra T. ^{[2
,11
]}

Mina, Kym ^{[12
,13
]}

Sivadorai, Padma ^{[14
]}

Davis, Mark R. ^{[14
]}

Allcock, Richard J. N. ^{[13
,15
]}

Kresoje, Nina ^{[13
,15
,16
]}

Laing, Nigel G. ^{[17
,18
]}

Thorburn, David R. ^{[19
,20
,21
]}

Slama, Abdelhamid ^{[1
]}

Christodoulou, John ^{[2
,10
,22
]}

Rustin, Pierre ^{[3
,4
]}

机构：

[1] Hop Bicetre, AP HP, Lab Biochim, F-94275 Le Kremlin Bicetre, France

[2] Univ Sydney, Sydney Med Sch, Discipline Paediat, Camperdown, NSW 2006, Australia

[3] Hop Robert Debre, Inst Natl Sante & Rech Med Unite Mixte Rech 676, F-75019 Paris, France

[4] Univ Paris 07, Fac Med Denis Diderot, F-75019 Paris, France

[5] Hop Robert Debre, AP HP, Reference Ctr Inherited Metab Dis, F-75019 Paris, France

[6] Columbia Univ, Dept Biol Sci, New York, NY 10027 USA

[7] Inst Cochin, Inst Natl Sante & Rech Med Unite Mixte 1016, F-75014 Paris, France

[8] Hop La Pitie Salpetriere, AP HP, Serv Biochim Metabol, F-75651 Paris, France

[9] Hop La Pitie Salpetriere, AP HP, Ctr Genet Mol & Chromosom, F-75651 Paris, France

[10] Childrens Hosp Westmead, Kids Res Inst, Genet Metab Disorders Res Unit, Westmead, NSW 2145, Australia

[11] Childrens Hosp Westmead, Inst Neurosci & Muscle Res, Westmead, NSW 2145, Australia

[12] Royal Perth Hosp, Dept Mol Genet, PathWest Lab Med WA, Perth, WA 6000, Australia

[13] Univ Western Australia, Sch Pathol & Lab Med, Nedlands, WA 6009, Australia

[14] Royal Perth Hosp, PathWest Lab Med WA, Dept Anatom Pathol, Neurogenet Lab, Perth, WA 6000, Australia

[15] Univ Western Australia, Lotterywest State Biomed Facil Genom, Nedlands, WA 6009, Australia

[16] Royal Perth Hosp, PathWest Lab Med WA, Dept Clin Immunol, Perth, WA 6000, Australia

[17] Univ Western Australia, Ctr Med Res, Nedlands, WA 6009, Australia

[18] Queen Elizabeth II Med Ctr, Westem Australian Inst Med Res, Nedlands, WA 6009, Australia

[19] Murdoch Childrens Res Inst, Victorian Clin Genet Serv, Melbourne, Vic, Australia

[20] Royal Childrens Hosp, Melbourne, Vic 3052, Australia

[21] Univ Melbourne, Dept Paediat, Melbourne, Vic 3010, Australia

[22] Univ Sydney, Sydney Med Sch, Camperdown, NSW 2006, Australia

来源：

AMERICAN JOURNAL OF HUMAN GENETICS | 2013年 / 93卷 / 02期

基金：

英国医学研究理事会; 美国国家卫生研究院; 澳大利亚国家健康与医学研究理事会;

关键词：

BC(1) COMPLEX; DEFICIENCY; MITOCHONDRIA; BCS1L; GENE;

D O I：

10.1016/j.ajhg.2013.06.015

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Many individuals with abnormalities of mitochondrial respiratory chain complex III remain genetically undefined. Here, we report mutations (c.288G>T [p.Trp96Cys] and c.643C>T [p.Leu215Phe]) in CYC1, encoding the cytochrome c(1) subunit of complex III, in two unrelated children presenting with recurrent episodes of ketoacidosis and insulin-responsive hyperglycemia. Cytochrome c(1), the heme-containing component of complex III, mediates the transfer of electrons from the Rieske iron-sulfur protein to cytochrome c. Cytochrome c(1) is present at reduced levels in the skeletal muscle and skin fibroblasts of affected individuals. Moreover, studies on yeast mutants and affected individuals' fibroblasts have shown that exogenous expression of wild-type CYC1 rescues complex III activity, demonstrating the deleterious effect of each mutation on cytochrome c(1) stability and complex III activity.

引用

页码：384 / 389

页数：6

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