Dataset Information

New MT-ND6 and NDUFA1 mutations in mitochondrial respiratory chain disorders.

ABSTRACT:

Objective

Mitochondrial respiratory chain disorder (MRCD) is an intractable disease of infants with variable clinical symptoms. Our goal was to identify the causative mutations in MRCD patients.

Methods

The subjects were 90 children diagnosed with MRCD by enzyme assay. We analyzed whole mitochondrial DNA (mtDNA) sequences. A cybrid study was performed in two patients. Whole exome sequencing was performed for one of these two patients whose mtDNA variant was confirmed as non-pathogenic.

Results

Whole mtDNA sequences identified 29 mtDNA variants in 29 patients (13 were previously reported, the other 13 variants and three deletions were novel). The remaining 61 patients had no pathogenic mutations in their mtDNA. Of the 13 patients harboring unreported mtDNA variants, we excluded seven variants by manual curation. Of the remaining six variants, we selected two Leigh syndrome patients whose mitochondrial enzyme activity was decreased in their fibroblasts and performed a cybrid study. We confirmed that m.14439G>A (MT-ND6) was pathogenic, while m.1356A>G (mitochondrial 12S rRNA) was shown to be a non-pathogenic polymorphism. Exome sequencing and a complementation study of the latter patient identified a novel c.55C>T hemizygous missense mutation in the nuclear-encoded gene NDUFA1.

Interpretation

Our results demonstrate that it is important to perform whole mtDNA sequencing rather than only typing reported mutations. Cybrid assays are also useful to diagnose the pathogenicity of mtDNA variants, and whole exome sequencing is a powerful tool to diagnose nuclear gene mutations as molecular diagnosis can provide a lead to appropriate genetic counseling.

SUBMITTER: Uehara N

PROVIDER: S-EPMC4184687 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Publications

New MT-ND6 and NDUFA1 mutations in mitochondrial respiratory chain disorders.

Uehara Natsumi N Mori Masato M Tokuzawa Yoshimi Y Mizuno Yosuke Y Tamaru Shunsuke S Kohda Masakazu M Moriyama Yohsuke Y Nakachi Yutaka Y Matoba Nana N Sakai Tetsuro T Yamazaki Taro T Harashima Hiroko H Murayama Kei K Hattori Keisuke K Hayashi Jun-Ichi J Yamagata Takanori T Fujita Yasunori Y Ito Masafumi M Tanaka Masashi M Nibu Ken-Ichi K Ohtake Akira A Okazaki Yasushi Y

Annals of clinical and translational neurology 20140428 5

<h4>Objective</h4>Mitochondrial respiratory chain disorder (MRCD) is an intractable disease of infants with variable clinical symptoms. Our goal was to identify the causative mutations in MRCD patients.<h4>Methods</h4>The subjects were 90 children diagnosed with MRCD by enzyme assay. We analyzed whole mitochondrial DNA (mtDNA) sequences. A cybrid study was performed in two patients. Whole exome sequencing was performed for one of these two patients whose mtDNA variant was confirmed as non-pathog ...[more]

PMID: 25356405

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Dataset Information

New MT-ND6 and NDUFA1 mutations in mitochondrial respiratory chain disorders.

Objective

Methods

Results

Interpretation

Publications

New MT-ND6 and NDUFA1 mutations in mitochondrial respiratory chain disorders.

Similar Datasets

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