Dataset Information

Case Report: Two Novel L1CAM Mutations in Two Unrelated Chinese Families With X-Linked Hydrocephalus.

ABSTRACT: L1 cell adhesion molecule is a type I transmembrane glycoprotein belonging to the immunoglobulin superfamily. Pathogenic mutations of L1CAM can cause L1 syndrome, referred to as a variety of disease spectrums characterized by hydrocephalus. In the present study, we reported two novel variants of L1CAM in two unrelated Chinese families with fetal hydrocephalus history. The woman of family 1, with three consecutive adverse birth histories of male fetuses with hydrocephalus, was identified by an exome sequence with a heterozygous mutation in the L1CAM gene, NM_000425.4: c.1696_1703 + 14del (p. S566Vfs*35), which was predicted to be pathogenic. It is predicted to disrupt RNA splicing and likely leads to an absent or disrupted protein product. In family 2, the mother, previously with once a voluntary termination of pregnancy owning to the fetus with hydrocephalus, was pregnant with a fetus with hydrocephalus in her second pregnancy. After fetal blood sampling, a pathogenic deletion of 1511bp in L1CAM, chromosome X: 153131395-153132905(hg19/GRCh37)/NM_000425.4: c.2043_2432-121del1511 leading to deletion of fibronectin type-III repeats I-II, was identified in the fetus with hydrocephalus inherited from the mother by an exome sequence. On her third pregnancy, a healthy female fetus was born without the L1CAM variant by preimplantation genetic testing for the monogenic disorder. This study emphasizes the importance of ultrasonic manifestation and family history of fetal hydrocephalus for L1CAM diagnosis. Our study expands the genotypes of L1CAM and aids the genetic counseling of fetal hydrocephalus and even preimplantation genetic testing for the monogenic disorder.

SUBMITTER: Zhou H

PROVIDER: S-EPMC9099044 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Case Report: Two Novel L1CAM Mutations in Two Unrelated Chinese Families With X-Linked Hydrocephalus.

Zhou Hang H Yu Qiuxia Q Li Yingsi Y Fu Fang F Li Ru R Chen Guilan G Wang Dan D Lu Yan Y Yang Xin X Li Dongzhi D Liao Can C

Frontiers in genetics 20220429

L1 cell adhesion molecule is a type I transmembrane glycoprotein belonging to the immunoglobulin superfamily. Pathogenic mutations of L1CAM can cause L1 syndrome, referred to as a variety of disease spectrums characterized by hydrocephalus. In the present study, we reported two novel variants of L1CAM in two unrelated Chinese families with fetal hydrocephalus history. The woman of family 1, with three consecutive adverse birth histories of male fetuses with hydrocephalus, was ident ...[more]

PMID: 35571029

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Project description:Background : Primary ciliary dyskinesia (PCD) is a rare genetic disorder, predominantly autosomal recessive. The dynein axonemal assembly factor 4 (DNAAF4) is mainly involved in the preassembly of multisubunit dynein protein, which is fundamental to the proper functioning of cilia and flagella. There are few reports of PCD-related pathogenic variants of DNAAF4, and almost no DNAAF4-related articles focused on sperm phenotype. Moreover, the association between DNAAF4 and scoliosis has never been reported, to the best of our knowledge. Materials and Methods: We recruited two patients with a clinical diagnosis of PCD. One came from a consanguineous and another from a non-consanguineous family. Clinical data, laboratory test results, and imaging data were analyzed. Through whole exome sequencing, immunofluorescence, electron microscopy, high-speed video microscopy analysis, and hematoxylin-eosin (HE) staining, we identified the disease-associated variants and validated the pathogenicity. Results: Proband 1 (P1, F1: II-1), a 19-year-old man, comes from a non-consanguineous family-I, and proband 2 (P2, F2: II-1), a 37-year-old woman, comes from a consanguineous family-II. Both had sinusitis, bronchiectasis, situs inversus, and scoliosis. P1 also had asthenoteratozoospermia, and P2 had an immature uterus. Two homozygous pathogenic variants in DNAAF4 (NM_130810.4), c.988C > T, p.(Arg330Trp), and DNAAF4 (NM_130810.4), c.733 C > T, p.(Arg245*), were identified through whole exome sequencing. High-speed microscopy analysis showed that most of the cilia were static in P1, with complete static of the respiratory cilia in P2. Immunofluorescence showed that the outer dynein arms (ODA) and inner dynein arms (IDA) were absent in the respiratory cilia of both probands, as well as in the sperm flagellum of P1. Transmission electron microscopy revealed the absence of ODA and IDA of respiratory cilia of P2, and HE staining showed irregular, short, absent, coiled, and bent flagella. Conclusion: Our study identified a novel variant c.733C > T, which expanded the spectrum of DNAAF4 variants. Furthermore, we linked DNAAF4 to asthenoteratozoospermia and likely scoliosis in patients with PCD. This study will contribute to a better understanding of PCD.

Dataset Information

Case Report: Two Novel L1CAM Mutations in Two Unrelated Chinese Families With X-Linked Hydrocephalus.

Publications

Case Report: Two Novel <i>L1CAM</i> Mutations in Two Unrelated Chinese Families With X-Linked Hydrocephalus.

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