Molecular basis of infantile reversible cytochrome c oxidase deficiency myopathy

被引：79

作者：

Horvath, Rita ^{[1
]}

Kemp, John P. ^{[1
]}

Tuppen, Helen A. L. ^{[1
]}

Hudson, Gavin ^{[1
]}

Oldfors, Anders ^{[2
]}

Marie, Suely K. N. ^{[3
]}

Moslemi, Ali-Reza ^{[2
]}

Servidei, Serenella ^{[4
]}

Holme, Elisabeth ^{[5
]}

Shanske, Sara ^{[6
]}

Kollberg, Gittan ^{[5
]}

Jayakar, Parul ^{[7
]}

Pyle, Angela ^{[1
]}

Marks, Harold M. ^{[8
]}

Holinski-Feder, Elke ^{[9
]}

Scavina, Mena ^{[10
]}

Walter, Maggie C. ^{[11
]}

Coku, Jorida

Guenther-Scholz, Andrea

Smith, Paul M. ^{[1
]}

McFarland, Robert ^{[1
]}

Chrzanowska-Lightowlers, Zofia M. A. ^{[1
]}

Lightowlers, Robert N. ^{[1
]}

Hirano, Michio ^{[6
]}

Lochmueller, Hanns ^{[12
]}

Taylor, Robert W. ^{[1
]}

Chinnery, Patrick F. ^{[1
]}

Tulinius, Mar ^{[13
]}

DiMauro, Salvatore ^{[6
]}

机构：

[1] Newcastle Univ, Sch Med, Inst Ageing & Hlth, Mitochondrial Res Grp, Framlington Pl, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England

[2] Univ Gothenburg, Sahlgrenska Acad, Dept Pathol, SE-41345 Gothenburg, Sweden

[3] Univ Sao Paulo, Sch Med, Dept Neurol, BR-04023900 Sao Paulo, Brazil

[4] Univ Cattolica Sacro Cuore, Dept Neurol, I-00168 Rome, Italy

[5] Univ Gothenburg, Sahlgrenska Acad, Dept Clin Chem, SE-41345 Gothenburg, Sweden

[6] Columbia Univ, Med Ctr, Dept Neurol, New York, NY 10032 USA

[7] Miami Childrens Hosp, Dr John McDonald Fdn, Ctr Med Genet, Miami, FL 33155 USA

[8] St Christophers Hosp Children, Dept Neurol, Philadelphia, PA 19134 USA

[9] Ctr Med Genet, D-80335 Munich, Germany

[10] Alfred I duPont Hosp Children, Div Neurol, Wilmington, DE 19803 USA

[11] Univ Munich, Dept Neurol, Friedrich Baur Inst, D-80336 Munich, Germany

[12] Newcastle Univ, Inst Human Genet, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England

[13] Univ Gothenburg, Sahlgrenska Acad, Dept Pediat, SE-41345 Gothenburg, Sweden

来源：

BRAIN | 2009年 / 132卷

基金：

英国生物技术与生命科学研究理事会; 英国惠康基金; 英国医学研究理事会;

关键词：

mitochondrial myopathy; reversible COX deficiency; homoplasmic tRNA mutation; MITOCHONDRIAL MYOPATHY; DIAGNOSIS; MUTATION; DISEASE; ENCEPHALOMYOPATHIES; PREVALENCE; DEPLETION;

D O I：

10.1093/brain/awp221

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Childhood-onset mitochondrial encephalomyopathies are usually severe, relentlessly progressive conditions that have a fatal outcome. However, a puzzling infantile disorder, long known as 'benign cytochrome c oxidase deficiency myopathy' is an exception because it shows spontaneous recovery if infants survive the first months of life. Current investigations cannot distinguish those with a good prognosis from those with terminal disease, making it very difficult to decide when to continue intensive supportive care. Here we define the principal molecular basis of the disorder by identifying a maternally inherited, homoplasmic m.14674T > C mt-tRNA(Glu) mutation in 17 patients from 12 families. Our results provide functional evidence for the pathogenicity of the mutation and show that tissue-specific mechanisms downstream of tRNA(Glu) may explain the spontaneous recovery. This study provides the rationale for a simple genetic test to identify infants with mitochondrial myopathy and good prognosis.

引用

页码：3165 / 3174

页数：10

共 27 条

[1] Quantitative PCR analysis of mitochondrial DNA content in patients with mitochondrial disease [J].