title: Mutation in SNAP25 as a novel genetic cause of epilepsy and intellectual disability.
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.
authors.affiliation: Children's Hospital of New York; New York City, NY USA.
authors.forename: Luis
authors.initials: L
authors.lastname: Rohena
authors.affiliation: Ambry Genetics; Aliso Viejo, CA USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Neidich
authors.affiliation: Children's Hospital of New York; New York City, NY USA.
authors.forename: Megan
authors.initials: M
authors.lastname: Truitt Cho
authors.affiliation: Ambry Genetics; Aliso Viejo, CA USA.
authors.forename: Kelly Df
authors.initials: KD
authors.lastname: Gonzalez
authors.affiliation: Ambry Genetics; Aliso Viejo, CA USA.
authors.forename: Sha
authors.initials: S
authors.lastname: Tang
authors.affiliation: New York University; New York City, NY USA.
authors.forename: Orrin
authors.initials: O
authors.lastname: Devinsky
authors.affiliation: Columbia University Medical Center; New York City, NY USA.
authors.forename: Wendy K
authors.initials: WK
authors.lastname: Chung
keywords: SNAP25; epilepsy; intellectual disability; novel mutation; whole exome sequencing