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Studying ultra-rare variants in STX1A uncovers a novel neurodevelopmental disorder

European Journal of Human Genetics (2023)Cite this article

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The proper functioning of the brain depends on the ability of neurons to communicate with each other. This communication is primarily mediated by chemical synaptic transmission, a process in which neurotransmitters are tightly packaged and released from one neuron to another through vesicle exocytosis. SNARE (soluble NSF attachment protein receptor) complexes are the engines that drive vesicle exocytosis, thus acting as major players in synaptic transmission [1, 2]. In a recent article by Luppe et al. [3], the authors compiled data from eight individuals harboring ultra-rare mutations in the gene STX1A, which encodes for a core component of the SNARE complex, and defined a novel neurodevelopmental disorder with or without epilepsy. Using in silico structural modeling, the authors also proposed potential pathogenic mechanisms for these mutations. Previously, only one mutation in STX1A had been published as a candidate mutation for a neurodevelopmental disorder in a consanguineous family [4]. Therefore, the study by Lupe et al. is the first to compile several variants in this gene and link them to putative pathogenic mechanisms. This work contributes to the body of knowledge on SNAREopathies, a group of rare diseases of diverse symptomatology caused by mutations affecting the components of the SNARE complex [5].

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  1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA

    Esmeralda Villavicencio Gonzalez & Ryan S. Dhindsa

  2. Jan and Dan Duncan Neurologic Research Institute at Texas Children’s Hospital, Houston, TX, USA

    Esmeralda Villavicencio Gonzalez & Ryan S. Dhindsa

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  1. Esmeralda Villavicencio Gonzalez
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  2. Ryan S. Dhindsa
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The article was written and conceptualized by E.V.G. and R.S.D.

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Correspondence to Esmeralda Villavicencio Gonzalez or Ryan S. Dhindsa.

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E.V.G. has no outside disclosures. R.S.D. is a paid consultant for AstraZeneca.

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Villavicencio Gonzalez, E., Dhindsa, R.S. Studying ultra-rare variants in STX1A uncovers a novel neurodevelopmental disorder. Eur J Hum Genet (2023). https://doi.org/10.1038/s41431-023-01348-2

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