A new frameshift mutation in L1CAM producing X-linked hydrocephalus

Mol Genet Genomic Med. 2020 Jan;8(1):e1031. doi: 10.1002/mgg3.1031. Epub 2019 Nov 22.

Abstract

Background: X-linked hydrocephalus (XLH), characterized by mental retardation and bilateral adducted thumbs, often come out to be a genetic disorder of L1CAM. It codes the protein L1 cell adhesion molecule (L1CAM), playing a crucial role in the development of the nervous system. The objective of the study was to report a new disease-causing mutation site of L1CAM, and gain further insight into the pathophysiology of hydrocephalus.

Methods: We collect the samples of a couple and their second hydrocephalic fetus. Then, the whole-exome sequencing and in-depth mutation analysis were performed.

Results: The variant c.2491delG (p.V831fs), located in the exon 19 of L1CAM (chrX:153131214), could damage the L1CAM function by producing a frameshift in the translation of fibronectin type-III of L1CAM.

Conclusion: We identified a novel disease-causing mutation in L1CAM for the first time, which further confirmed L1CAM as a gene underlying XLH cases.

Keywords: L1CAM; X-linked hydrocephalus; frameshift mutation.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cerebral Aqueduct / abnormalities*
  • Cerebral Aqueduct / pathology
  • Female
  • Fetus / abnormalities
  • Frameshift Mutation*
  • Genetic Diseases, X-Linked / genetics*
  • Genetic Diseases, X-Linked / pathology
  • Humans
  • Hydrocephalus / genetics*
  • Hydrocephalus / pathology
  • Male
  • Neural Cell Adhesion Molecule L1 / genetics*
  • Pedigree
  • Pregnancy

Substances

  • L1CAM protein, human
  • Neural Cell Adhesion Molecule L1

Supplementary concepts

  • Hydrocephalus, X-linked