Diagnosis of mitochondrial disorders by concomitant next-generation sequencing of the exome and mitochondrial genome.
Document Type
Article
Publication Date
9-1-2013
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.
Publisher
Academic Press
Publication Title
Genomics
ISSN
1089-8646
Volume
102
Issue
3
First Page
148
Last Page
156
Recommended Citation
Dinwiddie, Darrell L; Laurie D Smith; Neil A Miller; Andrea M Atherton; Emily G Farrow; Meghan E Strenk; Sarah E Soden; Carol J Saunders; and Stephen F Kingsmore.
"Diagnosis of mitochondrial disorders by concomitant next-generation sequencing of the exome and mitochondrial genome.."
Genomics
