A novel nonsense mutation in the L1CAM gene responsible for X-linked congenital hydrocephalus
Dewei Guo1,2, Yuting Shi3, Wenyan Jian1,2
1Department of Gynaecology and Obstetrics, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Insights
A novel mutation in the L1CAM gene was identified as the cause of severe congenital hydrocephalus in a fetus. This finding highlights the importance of L1CAM gene screening for prenatal diagnosis in families with a history of hydrocephalus.
Area of Science:
- Genetics
- Developmental Biology
- Medical Diagnostics
Background:
- Congenital hydrocephalus presents with diverse causes, including genetic mutations.
- Mutations in the L1CAM gene are a primary genetic cause, accounting for a significant portion of X-linked congenital hydrocephalus.
Purpose of the Study:
- To investigate the genetic cause of severe congenital hydrocephalus in a fetus with a family history of the condition.
- To identify the specific genetic mutation responsible for hydrocephalus in the presented case.
Main Methods:
- Whole-exome sequencing and Sanger sequencing were employed to analyze the fetal DNA.
- Magnetic resonance imaging, autopsy, and electron microscopy were used to characterize the phenotypic presentation.
Main Results:
- A novel maternally derived nonsense mutation (c.2865G>A; p. Y955*) in the L1CAM gene was identified in the fetus.
- The fetus exhibited severe hydrocephalus with significant lateral ventricle dilatation.
- Electron microscopy revealed an absence of ependymal cilia on the lateral ventricle walls.
Conclusions:
- L1CAM mutation screening is recommended for male fetuses with isolated hydrocephalus, particularly when there is a family history.
- Identifying L1CAM mutations can aid in the prenatal diagnosis of congenital hydrocephalus in subsequent pregnancies.
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.
More Related Videos
Related Concept Videos
01:31Immunoglobulin-like Cell Adhesion Molecules
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...
02:27Nonsense-mediated mRNA Decay
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
01:43Sex-linked Disorders
02:39lncRNA - Long Non-coding RNAs
02:41Lethal Alleles
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
01:19X-linked Traits