Novel mutations in the NDUFS1 gene cause low residual activities in human complex I deficiencies

被引：50

作者：

Hoefs, Saskia J. G. ^{[1
]}

Skjeldal, Ola H. ^{[2
,3
]}

Rodenburg, Richard J. ^{[1
]}

Nedregaard, Bard ^{[4
]}

van Kaauwen, Edwin P. M. ^{[1
]}

Spiekerkoetter, Ute ^{[5
]}

von Kleist-Retzow, Juergen-Christoph ^{[5
]}

Smeitink, Jan A. M. ^{[1
]}

Nijtmans, Leo G. ^{[1
]}

van den Heuvel, Lambert P. ^{[1
]}

机构：

[1] Radboud Univ Nijmegen, Med Ctr, Nijmegen Ctr Mitochondrial Disorders, Dept Pediat, NL-6500 HB Nijmegen, Netherlands

[2] Innlandet Hosp Thrust, Dept Med Res, Brumuddal, Norway

[3] Innlandet Hosp Thrust, Dept Pediat, Brumuddal, Norway

[4] Univ Oslo, Rikshosp, Oslo Univ Hosp, Neuroradiol Dept, N-0027 Oslo, Norway

[5] Univ Cologne, Univ Childrens Hosp, Dept Gen Pediat, Cologne, Germany

来源：

MOLECULAR GENETICS AND METABOLISM | 2010年 / 100卷 / 03期

关键词：

OXPHOS; Complex I; NDUFS1; Assembly; Residual activity; OXIDATIVE-PHOSPHORYLATION; MITOCHONDRIAL; SUBUNITS; NADH; ELECTROPHORESIS; OXIDOREDUCTASE; PATHOLOGY; POINT; DNA;

D O I：

10.1016/j.ymgme.2010.03.015

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Mitochondrial complex I deficiency is the most frequently encountered defect of the oxidative phosphorylation system. To identify the genetic cause of the complex! deficiency, we screened the gene encoding the NDUFS1 subunit. We report 3 patients with low residual complex I activity expressed in cultured fibroblasts, which displayed novel mutations in the NDUFS1 gene. One mutation introduces a premature stop codon, 3 mutations cause a substitution of amino acids and another mutation a deletion of one amino acid. The fibroblasts of the patients display a decreased amount and activity of complex I. In addition, a disturbed assembly pattern was observed. These results suggest that NDUFS1 is a prime candidate to screen for disease-causing mutations in patients with a very low residual complex I activity in cultured fibroblasts. (C) 2010 Elsevier Inc. All rights reserved.

引用

页码：251 / 256

页数：6

共 22 条

[1] Large-scale deletion and point mutations of the nuclear NDUFV1 and NDUFS1 genes in mitochondrial complex I deficiency [J].