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

BMC Medical Genetics

Penelope E Bonnen¹  Richard Alan Lewis⁵  Fernando Scaglia³  Lee-Jun Wong²  Brett H Graham²  William J Craigen⁴ 

[1] Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA;Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA;Texas Children’s Hospital, Clinical Care Center, Houston, Texas, USA;Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA;Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, USA

关键词: Genocopy;    Diagnostics;    SETX;    OCRL;    Lowe syndrome;    Encephalomyopathy;   

Others  :  1122672
DOI  :  10.1186/1471-2350-14-83

 received in 2012-11-02, accepted in 2013-08-06,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Craigen et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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