Identification and functional characteristics of a novel splice site variant in L1CAM caused X-linked hydrocephalus

This study identified the variant c.1380-1G > A in <i>L1CAM</i> as new pathogenic mutation for the first time according to ACMG/AMP (American College of Medical Genetics and Genomics and the Association for Molecular Pathology)-based guidelines, which caused severe fetal X-linked hydrocephalus and partial agenesis of corpus callosum. This discovery expands the mutational landscape of <i>L1CAM</i>-associated disorders, highlights the diagnostic utility of integrating WES into prenatal workflows for unresolved fetal anomalies, and provides actionable insights for genetic counseling in families at risk of X-linked hydrocephalus.