Mutations in Complex I Assembly Factor TMEM126B Result in Muscle Weakness and Isolated Complex I Deficiency.
Am J Hum Genet
; 99(1): 208-16, 2016 Jul 07.
Article
em En
| MEDLINE
| ID: mdl-27374773
ABSTRACT
Mitochondrial complex I deficiency results in a plethora of often severe clinical phenotypes manifesting in early childhood. Here, we report on three complex-I-deficient adult subjects with relatively mild clinical symptoms, including isolated, progressive exercise-induced myalgia and exercise intolerance but with normal later development. Exome sequencing and targeted exome sequencing revealed compound-heterozygous mutations in TMEM126B, encoding a complex I assembly factor. Further biochemical analysis of subject fibroblasts revealed a severe complex I deficiency caused by defective assembly. Lentiviral complementation with the wild-type cDNA restored the complex I deficiency, demonstrating the pathogenic nature of these mutations. Further complexome analysis of one subject indicated that the complex I assembly defect occurred during assembly of its membrane module. Our results show that TMEM126B defects can lead to complex I deficiencies and, interestingly, that symptoms can occur only after exercise.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Debilidade Muscular
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Doenças Mitocondriais
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Complexo I de Transporte de Elétrons
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Proteínas de Membrana
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Mutação
Limite:
Adolescent
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Adult
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Child
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Humans
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Infant
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Male
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article