Diagnosis and molecular basis of mitochondrial respiratory chain disorders: exome sequencing for disease gene identification.
Mitochondrial disorders have the highest incidence among congenital metabolic diseases, and are thought to occur at a rate of 1 in 5000 births. About 25% of the diseases diagnosed as mitochondrial disorders in the field of pediatrics have mitochondrial DNA abnormalities, while the rest occur due to defects in genes encoded in the nucleus. The most important function of the mitochondria is biosynthesis of ATP. Mitochondrial disorders are nearly synonymous with mitochondrial respiratory chain disorder, as respiratory chain complexes serve a central role in ATP biosynthesis. By next-generation sequencing of the exome, we analyzed 104 patients with mitochondrial respiratory chain disorders. The results of analysis to date were 18 patients with novel variants in genes previously reported to be disease-causing, and 27 patients with mutations in genes suggested to be associated in some way with mitochondria, and it is likely that they are new disease-causing genes in mitochondrial disorders. This article is part of a Special Issue entitled Frontiers of Mitochondrial Research.
Department of Pediatrics, Faculty of Medicine, Saitama Medical University, Saitama 350-0495, Japan. Electronic address: akira_oh@saitama-med.ac.jp.
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Ohtake
Department of Metabolism, Chiba Children's Hospital, Chiba 266-0007, Japan.
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Murayama
Department of Pediatrics, Jichi Medical University, Tochigi 329-0498, Japan.
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Mori
Department of Pediatrics, Faculty of Medicine, Saitama Medical University, Saitama 350-0495, Japan.
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Harashima
Department of Pediatrics, Faculty of Medicine, Saitama Medical University, Saitama 350-0495, Japan.
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Yamazaki
Research Center for Genomic Medicine, Saitama Medical University, Saitama 350-0495, Japan.
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Tamaru
Research Center for Genomic Medicine, Saitama Medical University, Saitama 350-0495, Japan.
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Yamashita
Research Center for Genomic Medicine, Saitama Medical University, Saitama 350-0495, Japan.
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Kishita
Research Center for Genomic Medicine, Saitama Medical University, Saitama 350-0495, Japan.
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Nakachi
Research Center for Genomic Medicine, Saitama Medical University, Saitama 350-0495, Japan.
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Kohda
Research Center for Genomic Medicine, Saitama Medical University, Saitama 350-0495, Japan.
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Tokuzawa
Research Center for Genomic Medicine, Saitama Medical University, Saitama 350-0495, Japan.
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Mizuno
Research Center for Genomic Medicine, Saitama Medical University, Saitama 350-0495, Japan.
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Moriyama
Research Center for Genomic Medicine, Saitama Medical University, Saitama 350-0495, Japan.
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Kato
Research Center for Genomic Medicine, Saitama Medical University, Saitama 350-0495, Japan.
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Okazaki
D002467:Cell Nucleus / Q000235:genetics; D059472:Exome / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D046228:Microarray Analysis; D028361:Mitochondrial Diseases / Q000175:diagnosis* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA
Blue native polyacrylamide gel; Electrophoresis; Exome sequencing; Mitochondrial respiratory chain disorder; Narrowing down protocol