Novel Splice Site Pathogenic Variant in STXBP1 Gene in a Child with Intellectual Disability, Epilepsy, and Autism Spectrum Disorder: A Case Report

Abstract

<b><i>Introduction:</i></b> Pathogenic variants in the <i>STXBP1</i> gene are associated to a large spectrum of severe early onset developmental and epileptic encephalopathies (OMIM #612164). They were also identified in various other neurodevelopmental disorders. This gene encodes for the syntaxin-binding protein 1, a member of the SEC-1 family of membrane-transport proteins that modulate the presynaptic vesicular fusion by interacting with soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). However, the physiopathology of <i>STXBP1</i> pathogenic variants is not yet fully understood. <b><i>Case Presentation:</i></b> Herein, we report a patient presenting intellectual disability, early onset seizures, and autism. Clinical exome sequencing identified a novel monoallelic splice pathogenic variant <i>STXBP1</i>(NM_001032221.6):c.38–2A>G. <b><i>Discussion:</i></b> Splice-site pathogenic variants in the <i>STXBP1</i> gene are mostly associated with West syndrome, early onset epilepsy and encephalopathy, and Ohtahara syndrome. Our findings extend clinical and molecular spectrum of <i>STXBP1</i> gene variants by reporting the first splice-site variant associated with autism along with early onset epilepsy and, and intellectual disability in a patient.