A novel nonsense mutation in the <i>L1CAM</i> gene responsible for X‐linked congenital hydrocephalus

Abstract

BACKGROUND: Congenital hydrocephalus is a descriptive diagnosis of symptoms, that are present for numerous reasons, including chromosomal disorders, genetic mutations, intrauterine infection and hemorrhage, amongst other factors. Mutation of L1CAM gene is the most frequent cause of congenital hydrocephalus, contributing to approximately 30% of X-linked congenital hydrocephalus. METHODS: In the present study, we used whole-exome sequencing and Sanger sequencing to investigate an aborted male fetus present with severe congenital hydrocephalus at 24 weeks of gestation, whose mother had a history of two previous voluntary terminations of pregnancies as a result of hydrocephalus. Magnetic resonance imaging, an autopsy and electron microscopy were performed and the phenotypic changes were described. RESULTS: Whole-exome sequencing in the fetus, as well as variant segregation analysis, revealed a novel maternally derived hemizygous nonsense mutation (c.2865G>A; p. Y955*) in exon 21 of the L1CAM gene (NM_000425.4). Severe hydrocephalus was observed along with marked dilatation of lateral ventricles. An electron micrograph of the surface of lateral ventricle walls revealed a lack of ependymal cilia. CONCLUSION: The present study suggests that L1CAM mutation screening should be considered for a male fetus with isolated hydrocephalus, especially with a family history, which could facilitate prenatal diagnosis in a subsequent pregnancy.