Abstract
STXBP1 (Munc18-1) is a component of the machinery involved in the fusion of secretory vesicles to the presynaptic membrane for the release of neurotransmitters. De novo missense mutations in STXBP1 were recently reported in patients with Ohtahara syndrome, a form of encephalopathy with severe early-onset epilepsy. In addition, sequencing of the coding region of STXBP1 in 95 patients with non-syndromic intellectual disability (NSID) revealed de novo truncating mutations in two patients who also showed severe non-specific epilepsy, suggesting that STXBP1 disruption has the potential of causing a wide spectrum of epileptic disorders in association with intellectual disability. Here, we report on the mutational screening of STXBP1 in a different series of 50 patients with NSID and the identification of a novel de novo truncating mutation (c.1206delT/ p.Y402X) in a male with NSID, but surprisingly with no history of epilepsy. This is the first report of a patient with a truncating mutation in STXBP1 that does not show epilepsy, thus, expanding the clinical spectrum associated with STXBP1 disruption.
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Acknowledgements
We thank the patients and their parents for participating to this study. We are grateful for the dedicated work of members of the S2D team (CHUM Research Center, Montreal), including management (Claude Marineau and Ronald G Lafrenière), bioinformatics (Edouard Henrion, Ousmane Diallo and Dan Spiegelman) and genetic screening divisions (Amelie Piton, Annie Raymond, Annie Levert, Pascale Thibodeau, Sandra Laurent and Karine Lachapelle). We are also thankful for the McGill University and Génome Québec Innovation Centre Sequencing (Pierre Lepage, Sébastien Brunet and Hao Fan Yam) and Bioinformatics (Louis Létourneau and Louis Dumond Joseph) groups. Supported by grants from the Canadian Institute of Health Research (CIHR; to JLM, GAR and JCL), Réseau de Génétique Médicale Appliquée/Fonds de la Recherche en Santé (FRSQ; to JLM), Genome Canada and Genome Quebec and co-funding by Université de Montréal for the S2D project (to GAR). JLM is a recipient of a Clinical Investigatorship Award of the CIHR (Institute of Genetics) and of a Senior Scientist Award from the FRSQ.
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Hamdan, F., Gauthier, J., Dobrzeniecka, S. et al. Intellectual disability without epilepsy associated with STXBP1 disruption. Eur J Hum Genet 19, 607–609 (2011). https://doi.org/10.1038/ejhg.2010.183
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DOI: https://doi.org/10.1038/ejhg.2010.183
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