|Title||Exome sequencing of a patient with suspected mitochondrial disease reveals a likely multigenic etiology.|
|Publication Type||Journal Article|
|Year of Publication||2013|
|Authors||Craigen, WJ, Graham, BH, Wong, L-J, Scaglia, F, Lewis, RAlan, Bonnen, PE|
|Journal||BMC Med Genet|
|Keywords||Adult, Computational Biology, Exome, Genetic Diseases, X-Linked, Genetic Loci, Homozygote, Humans, Male, Mitochondrial Diseases, Mutation, Missense, Nephrolithiasis, Oculocerebrorenal Syndrome, Pedigree, Phenotype, Phosphoric Monoester Hydrolases, RNA Helicases, RNA, Ribosomal, 16S, Sequence Analysis, DNA, Spinocerebellar Ataxias, Spinocerebellar Degenerations|
BACKGROUND: The clinical features of mitochondrial disease are complex and highly variable, leading to challenges in establishing a specific diagnosis. Despite being one of the most commonly occurring inherited genetic diseases with an incidence of 1/5000, ~90% of these complex patients remain without a DNA-based diagnosis. We report our efforts to identify the pathogenetic cause for a patient with typical features of mitochondrial disease including infantile cataracts, CPEO, ptosis, progressive distal muscle weakness, and ataxia who carried a diagnosis of mitochondrial disease for over a decade.
METHODS: Whole exome sequencing and bioinformatic analysis of these data were conducted on the proband.
RESULTS: Exome sequencing studies showed a homozygous splice site mutation in SETX, which is known to cause Spinocerebellar Ataxia, Autosomal Recessive 1 (SCAR1). Additionally a missense mutation was identified in a highly conserved position of the OCRL gene, which causes Lowe Syndrome and Dent Disease 2.
CONCLUSIONS: This patient's complex phenotype reflects a complex genetic etiology in which no single gene explained the complete clinical presentation. These genetic studies reveal that this patient does not have mitochondrial disease but rather a genocopy caused by more than one mutant locus. This study demonstrates the benefit of exome sequencing in providing molecular diagnosis to individuals with complex clinical presentations.
|Alternate Journal||BMC Med. Genet.|
|PubMed Central ID||PMC3751849|