Related Experiment Video

Updated: Jul 15, 2026

A Strategy to Identify de Novo Mutations in Common Disorders such as Autism and Schizophrenia
05:51

A Strategy to Identify de Novo Mutations in Common Disorders such as Autism and Schizophrenia

Published on: June 15, 2011

Novel Splice Site Pathogenic Variant in STXBP1 Gene in a Child with Intellectual Disability, Epilepsy, and Autism

Nada Amllal1,2, Jaber Lyahyai1,2, Siham Chafai Elalaoui1,2

  • 1Research Team in Genomics and Molecular Epidemiology of Genetic Diseases, Genomics Center of Human Pathologies, Faculty of Medicine and Pharmacy, University Mohammed V, Rabat, Morocco.

Molecular Syndromology
|October 3, 2024
PubMed

Insights

Pathogenic variants in the STXBP1 gene cause severe neurodevelopmental disorders. This study identifies a novel splice variant linked to autism, early-onset epilepsy, and intellectual disability, expanding the known STXBP1-related conditions.

Area of Science:

  • Genetics
  • Neuroscience
  • Molecular Biology

Background:

  • Pathogenic variants in the STXBP1 gene are linked to a range of severe early-onset developmental and epileptic encephalopathies.
  • STXBP1 encodes syntaxin-binding protein 1, crucial for presynaptic vesicular fusion via SNARE interactions.
  • The precise pathophysiology of STXBP1 variants remains incompletely understood.

Purpose of the Study:

  • To report a novel STXBP1 splice variant.
  • To expand the clinical and molecular spectrum of STXBP1-related neurodevelopmental disorders.
  • To investigate the association of STXBP1 variants with autism.

Main Methods:

  • Clinical exome sequencing was performed on a patient with intellectual disability, early-onset seizures, and autism.
  • A novel monoallelic splice pathogenic variant in STXBP1 (NM_001032221.6:c.38-2A>G) was identified.

Main Results:

  • The identified variant is a splice-site mutation in the STXBP1 gene.
  • This represents the first reported splice-site variant in STXBP1 associated with autism, alongside early-onset epilepsy and intellectual disability.
  • This finding broadens the known clinical presentations associated with STXBP1 gene variants.

Conclusions:

  • STXBP1 splice-site variants are associated with a broader spectrum of neurodevelopmental disorders than previously recognized.
  • The study highlights the importance of considering STXBP1 in patients with complex neurodevelopmental phenotypes including autism.
  • Further research is needed to elucidate the specific mechanisms underlying STXBP1 variant pathogenicity in diverse clinical contexts.
Abstract

Keywords:
AutismEpilepsyIntellectual disabilitySTXBP1 geneSplice pathogenic variant

More Related Videos

Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information09:37

Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information

Published on: August 15, 2019

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila06:41

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila

Published on: August 20, 2019

Related Concept Videos

Pleiotropy01:33

Pleiotropy

Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
RNA Splicing01:32

RNA Splicing

Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
Sex-linked Disorders01:43

Sex-linked Disorders

Like autosomes, sex chromosomes contain a variety of genes necessary for normal body function. When a mutation in one of these genes results in biological deficits, the disorder is considered sex-linked.
Alternative RNA Splicing02:18

Alternative RNA Splicing

Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
Single Nucleotide Polymorphisms-SNPs01:05

Single Nucleotide Polymorphisms-SNPs

A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
Autism Spectrum Disorder01:19

Autism Spectrum Disorder

Autism spectrum disorder (ASD) is a neurodevelopmental condition marked by persistent deficits in social communication and interaction alongside restrictive and repetitive behaviors or interests. ASD is sometimes accompanied by intellectual impairment.
These core symptoms manifest differently among individuals, ranging from mild to severe. The disorder's complexity extends beyond its clinical presentation, encompassing a diverse range of biological, cognitive, and sociocultural influences.