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Exome sequencing in Jewish and Arab patients with rhabdomyolysis reveals single-gene etiology in 43% of cases
- Source :
- Pediatric Nephrology. 32:2273-2282
- Publication Year :
- 2017
- Publisher :
- Springer Science and Business Media LLC, 2017.
-
Abstract
- Rhabdomyolysis is a clinical emergency that may cause acute kidney injury (AKI). It can be acquired or due to monogenic mutations. Around 60 different rare monogenic forms of rhabdomyolysis have been reported to date. In the clinical setting, identifying the underlying molecular diagnosis is challenging due to nonspecific presentation, the high number of causative genes, and current lack of data on the prevalence of monogenic forms. We employed whole exome sequencing (WES) to reveal the percentage of rhabdomyolysis cases explained by single-gene (monogenic) mutations in one of 58 candidate genes. We investigated a cohort of 21 unrelated families with rhabdomyolysis, in whom no underlying etiology had been previously established. Using WES, we identified causative mutations in candidate genes in nine of the 21 families (43%). We detected disease-causing mutations in eight of 58 candidate genes, grouped into the following categories: (1) disorders of fatty acid metabolism (CPT2), (2) disorders of glycogen metabolism (PFKM and PGAM2), (3) disorders of abnormal skeletal muscle relaxation and contraction (CACNA1S, MYH3, RYR1 and SCN4A), and (4) disorders of purine metabolism (AHCY). Our findings demonstrate a very high detection rate for monogenic etiologies using WES and reveal broad genetic heterogeneity for rhabdomyolysis. These results highlight the importance of molecular genetic diagnostics for establishing an etiologic diagnosis. Because these patients are at risk for recurrent episodes of rhabdomyolysis and subsequent risk for AKI, WES allows adequate prophylaxis and treatment for these patients and their family members and enables a personalized medicine approach.
- Subjects :
- Adult
0301 basic medicine
Candidate gene
Adolescent
Bioinformatics
Rhabdomyolysis
Article
03 medical and health sciences
0302 clinical medicine
Exome Sequencing
Humans
Medicine
Exome
Genetic Predisposition to Disease
Child
Exome sequencing
Genetics
business.industry
Genetic heterogeneity
medicine.disease
Arabs
030104 developmental biology
PFKM
Nephrology
Jews
Mutation
Pediatrics, Perinatology and Child Health
Etiology
Personalized medicine
business
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 1432198X and 0931041X
- Volume :
- 32
- Database :
- OpenAIRE
- Journal :
- Pediatric Nephrology
- Accession number :
- edsair.doi.dedup.....8f5efd13b5eb588dd6c1f91a8eb699c5