Combining whole-exome sequencing with deep clinical phenotyping (that is, clinical and biochemical evaluation) substantially increases the likelihood of obtaining a genetic diagnosis in patients with intellectual developmental disorder and unexplained metabolic abnormalities, according to a new study. Using this combined approach, a genetic diagnosis was obtained in 28 of 41 probands (68%), which included variants in novel genes, candidate genes and those known to cause the disease. Most variants were classified as either pathogenic or probably pathogenic. Importantly, genetic diagnosis altered the clinical treatment of 18 probands (44%), including treatments targeting the cellular or molecular defect. Further use of this approach could improve genetic diagnosis and subsequent management of patients with other neurometabolic disorders.
References
Tarailo-Graovac, M. et al. Exome sequencing and the management of neurometabolic disorders. N. Engl. J. Med. http://dx.doi.org/10.1056/NEJMoa1515792 (2016)
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Holmes, D. Exome sequencing aids targeted treatment of inborn errors of metabolism. Nat Rev Endocrinol 12, 436 (2016). https://doi.org/10.1038/nrendo.2016.96
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DOI: https://doi.org/10.1038/nrendo.2016.96