A De Novo Variant in Calponin2 Causes Intestinal Pseudo-obstruction: Evidence from Patient and Mouse Model

In brief

This study identifies a novel de novo variant in the Calponin2 gene as a cause of pediatric intestinal pseudo-obstruction (PIPO), a severe gastrointestinal motility disorder. Using patient data and mouse models, researchers establish Calponin2 as a new disease gene, advancing understanding of PIPO's genetic heterogeneity and potentially enabling better diagnosis for affected children.

• De novo CNN2 variant identified as novel genetic cause of pediatric intestinal pseudo-obstruction through patient sequencing and mouse modeling
• Calponin2 dysfunction impairs smooth muscle contractility in the gastrointestinal tract, establishing CNN2 as a PIPO disease gene
• Genetic testing for CNN2 variants should be considered in unexplained PIPO cases to improve diagnostic yield and genetic counseling
• Mouse models with CNN2 deficiency recapitulate human PIPO phenotype, validating pathogenic mechanism and enabling therapeutic research
• This discovery expands the genetic heterogeneity landscape of PIPO and may guide precision medicine approaches for affected patients

Written by the GCMD Library team from the article.