Common <i>cis</i>-regulatory variation modifies the penetrance of pathogenic <i>SHROOM3</i> variants in craniofacial microsomia.

ABSTRACT: Pathogenic coding variants have been identified in thousands of genes, yet the mechanisms underlying the incomplete penetrance in individuals carrying these variants are poorly understood. In this study, in a cohort of 2009 craniofacial microsomia (CFM) patients of Chinese ancestry and 2625 Han Chinese controls, we identified multiple predicted pathogenic coding variants in SHROOM3 in both CFM patients and healthy individuals. We found that the penetrance of CFM correlates with specific haplotype combinations containing likely pathogenic-coding SHROOM3 variants and CFM-associated expression quantitative trait loci (eQTLs) of SHROOM3 expression. Further investigations implicate specific eQTL combinations, such as rs1001322 or rs344131, in combination with other signific

SUBMITTER: Zhu H 

PROVIDER: S-EPMC12047249 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature