A novel nonsense mutation in the L1CAM gene responsible for X‐linked congenital hydrocephalus

Abstract

BackgroundCongenital 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.MethodsIn 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.ResultsWhole‐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.ConclusionThe 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.

Whole‑exome sequencing reveals MYH7 p.R671C mutation in three different phenotypes of familial hypertrophic cardiomyopathy

“…Extracted DNA samples were sent to Beijing Nuohe Zhiyuan Technology Co., Ltd. for WES. Genomic DNA was sheared into fragments with a length of 150-200 bp through sonication ( 17 ). End-repairing, A-tailing and adaptor ligation, a four-cycle pre-capture PCR amplification and xGen Exome Research Panel (Integrated DNA Technologies, Inc.) enrichment were then performed ( 17 ).…”

“…Genomic DNA was sheared into fragments with a length of 150-200 bp through sonication ( 17 ). End-repairing, A-tailing and adaptor ligation, a four-cycle pre-capture PCR amplification and xGen Exome Research Panel (Integrated DNA Technologies, Inc.) enrichment were then performed ( 17 ). The sequencing was performed on an Illumina Hiseq Xten platform (Illumina, Inc.) with a mean sequence coverage of ≥90X and a coverage of ≥20X in >95% of the target bases.…”

Prenatal diagnosis of a nonsense mutation in the L1CAM gene resulting in congenital hydrocephalus: A case report and literature review

“…Preliminary karyotype analysis and single-nucleotide polymorphism array did not provide any evidence (15). Whole-exome sequencing (WES) and in-depth mutation analysis were then used to analyze the samples from the parents and umbilical cord blood (16). All underlying pathogenic mutants were confirmed by Sanger sequencing (6).…”

“…A total of 11 publications related to the topic published between 1989 and October 25, 2020 were retrieved and their features are summarized in Table I. To date, 30 different nonsense mutations in the L1CAM gene have been reported (7,8,16,(18)(19)(20)(21)(22)(23)(24)(25)(26)(27).…”

L1CAM variants cause two distinct imaging phenotypes on fetal MRI

“…Postnatal imaging features include obstructive hydrocephalus, CCA, enlarged quadrigeminal plate, interthalamic adhesion hypertrophy, and vermian hypoplasia 2 . Moreover, data on fetal MRI are scarce with relevant implications for counseling and surgical planning 3–6 . In particular, little information is available on the prenatal appearance of midbrain–hindbrain structures in this condition.…”