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Exome sequencing of a patient with suspected mitochondrial disease reveals a likely multigenic etiology.


ABSTRACT: 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.Whole exome sequencing and bioinformatic analysis of these data were conducted on the proband.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.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.

SUBMITTER: Craigen WJ 

PROVIDER: S-EPMC3751849 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Exome sequencing of a patient with suspected mitochondrial disease reveals a likely multigenic etiology.

Craigen William J WJ   Graham Brett H BH   Wong Lee-Jun LJ   Scaglia Fernando F   Lewis Richard Alan RA   Bonnen Penelope E PE  

BMC medical genetics 20130816


<h4>Background</h4>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, prog  ...[more]

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