Elsevier

Genomics

Volume 102, Issue 3, September 2013, Pages 148-156
Genomics

Review
Diagnosis of mitochondrial disorders by concomitant next-generation sequencing of the exome and mitochondrial genome

https://doi.org/10.1016/j.ygeno.2013.04.013Get rights and content
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Highlights

  • Able to diagnose four patients with mitochondrial disorders through exome sequencing

  • Concomitantly sequenced the nuclear exome and mitochondrial genome

  • Accurately detected homoplasmic and heteroplasmic variants from the mtDNA

  • Exome sequencing produced a molecular dx when conventional molecular testing failed.

Abstract

Mitochondrial diseases are notoriously difficult to diagnose due to extreme locus and allelic heterogeneity, with both nuclear and mitochondrial genomes potentially liable. Using exome sequencing we demonstrate the ability to rapidly and cost effectively evaluate both the nuclear and mitochondrial genomes to obtain a molecular diagnosis for four patients with three distinct mitochondrial disorders. One patient was found to have Leigh syndrome due to a mutation in MT-ATP6, two affected siblings were discovered to be compound heterozygous for mutations in the NDUFV1 gene, which causes mitochondrial complex I deficiency, and one patient was found to have coenzyme Q10 deficiency due to compound heterozygous mutations in COQ2. In all cases conventional diagnostic testing failed to identify a molecular diagnosis. We suggest that additional studies should be conducted to evaluate exome sequencing as a primary diagnostic test for mitochondrial diseases, including those due to mtDNA mutations.

Keywords

Mitochondrial genome
Exome
Next-generation sequencing
Leigh syndrome
Homoplasmy
MT-ATP6
Lactic academia
Mitochondrial complex I
Inborn error of metabolism
CoQ10 deficiency
Molecular diagnostics

Cited by (0)

1

Authors contributed equally.

2

Fax: + 1 816 855 1958.

3

Fax: + 1 816 346 1378.

4

Fax: + 1 816 701 4854.

5

Fax: + 1 816 346 1382.