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. 2013 Sep 5:1:e26314.
doi: 10.4161/rdis.26314. eCollection 2013.

Mutation in SNAP25 as a novel genetic cause of epilepsy and intellectual disability

Luis Rohena  1 , Julie Neidich  2 , Megan Truitt Cho  1 , Kelly Df Gonzalez  2 , Sha Tang  2 , Orrin Devinsky  3 , Wendy K Chung  4
Affiliations

Mutation in SNAP25 as a novel genetic cause of epilepsy and intellectual disability

Luis Rohena et al. Rare Dis. .

Erratum in

  • Corrigendum.
    [No authors listed] [No authors listed] Rare Dis. 2015 Apr 16;3(1):e1037119. doi: 10.1080/21675511.2015.1037119. eCollection 2015. Rare Dis. 2015. PMID: 26484002 Free PMC article.

Abstract

Whole exome sequencing using a parent-child trio design to identify de novo mutations provides an efficient method to identify novel genes for rare diseases with low reproductive fitness that are difficult to study by more classical genetic methods of linkage analysis. We describe a 15 y old female with severe static encephalopathy, intellectual disability, and generalized epilepsy. After extensive metabolic and genetic testing, whole exome sequencing identified a novel de novo variant in Synaptosomal-associated protein-25 (SNAP25), c.142G > T p.Phe48Val alteration. This variant is predicted to be damaging by all prediction algorithms. SNAP25 is part of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein complex which is involved in exocytotic release of neurotransmitters. Genetic alterations in Snap25 in animal models can cause anxiety-related behavior, ataxia and seizures. We suggest that SNAP25 mutations in humans are a novel genetic cause of intellectual disability and epilepsy.

Keywords: SNAP25; epilepsy; intellectual disability; novel mutation; whole exome sequencing.

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Figures

None
Figure 1. (A) Family pedigree. Shaded shapes indicate affected individuals. (B) Next-gen sequence alignment of the SNAP25: c.142G > T (p.V48F alteration in the proband, mother, and father. (C) Sequence conservation plots at the mutated site amino acid position across different species.
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