Mutations in BCKD-kinase lead to a potentially treatable form of autism with epilepsy

G. Novarino, P. El Fishawy, H. Kayserili, N. Meguid, E. Scott, J. Schroth, J. Silhavy, M. Kara, R. Khalil, T. Ben Omran, A. Ercan Sencicek, A. Hashish, S. Sanders, A. Gupta, H. Hashem, D. Matern, S. Gabriel, L. Sweetman, Y. Rahimi, R. Harris, M. State, J. Gleeson, Science 338 (2012) 394–397.

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Abstract
Autism spectrum disorders are a genetically heterogeneous constellation of syndromes characterized by impairments in reciprocal social interaction. Available somatic treatments have limited efficacy. We have identified inactivating mutations in the gene BCKDK (Branched Chain Ketoacid Dehydrogenase Kinase) in consanguineous families with autism, epilepsy, and intellectual disability. The encoded protein is responsible for phosphorylation-mediated inactivation of the E1α subunit of branched-chain ketoacid dehydrogenase (BCKDH). Patients with homozygous BCKDK mutations display reductions in BCKDK messenger RNA and protein, E1α phosphorylation, and plasma branched-chain amino acids. Bckdk knockout mice show abnormal brain amino acid profiles and neurobehavioral deficits that respond to dietary supplementation. Thus, autism presenting with intellectual disability and epilepsy caused by BCKDK mutations represents a potentially treatable syndrome.
Publishing Year
Date Published
2012-10-19
Journal Title
Science
Volume
338
Issue
6105
Page
394 - 397
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Novarino G, El Fishawy P, Kayserili H, et al. Mutations in BCKD-kinase lead to a potentially treatable form of autism with epilepsy. Science. 2012;338(6105):394-397. doi:10.1126/science.1224631
Novarino, G., El Fishawy, P., Kayserili, H., Meguid, N., Scott, E., Schroth, J., … Gleeson, J. (2012). Mutations in BCKD-kinase lead to a potentially treatable form of autism with epilepsy. Science, 338(6105), 394–397. https://doi.org/10.1126/science.1224631
Novarino, Gaia, Paul El Fishawy, Hülya Kayserili, Nagwa Meguid, Eric Scott, Jana Schroth, Jennifer Silhavy, et al. “Mutations in BCKD-Kinase Lead to a Potentially Treatable Form of Autism with Epilepsy.” Science 338, no. 6105 (2012): 394–97. https://doi.org/10.1126/science.1224631.
G. Novarino et al., “Mutations in BCKD-kinase lead to a potentially treatable form of autism with epilepsy,” Science, vol. 338, no. 6105, pp. 394–397, 2012.
Novarino G, El Fishawy P, Kayserili H, Meguid N, Scott E, Schroth J, Silhavy J, Kara M, Khalil R, Ben Omran T, Ercan Sencicek A, Hashish A, Sanders S, Gupta A, Hashem H, Matern D, Gabriel S, Sweetman L, Rahimi Y, Harris R, State M, Gleeson J. 2012. Mutations in BCKD-kinase lead to a potentially treatable form of autism with epilepsy. Science. 338(6105), 394–397.
Novarino, Gaia, et al. “Mutations in BCKD-Kinase Lead to a Potentially Treatable Form of Autism with Epilepsy.” Science, vol. 338, no. 6105, American Association for the Advancement of Science, 2012, pp. 394–97, doi:10.1126/science.1224631.

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