Frontiers in immunology
Integrated genetic and functional analyses reveal the pathogenic effects of a novel STXBP3 variant in very-early-onset inflammatory bowel disease with immunodeficiency
By Pan C, Zhang P, Tang W and 7 others.
Abstract
Background
Very early onset inflammatory bowel disease (VEOIBD) is frequently driven by monogenic defects. Pathogenic variants in the syntaxin-binding protein 3 (STXBP3) gene have been implicated in VEOIBD; however, the relationship between specific variant types and clinical manifestations remains incompletely understood. This study aimed to identify the genetic cause in a patient with VEOIBD and explore the possible genotype-phenotype correlations of STXBP3-related disorders.
Methods
We performed trio-whole-exome sequencing (trio-WES) on a male infant presenting with VEOIBD, sensorineural hearing loss, and immunodeficiency. Functional consequences of the identified variant were investigated using RNA sequencing (RNA-seq), reverse transcription-polymerase chain reaction (RT-PCR), western blotting and co-immunoprecipitation (co-IP) assay. A systematic literature review was conducted to analyze clinical features and inheritance patterns across all reported STXBP3 cases.