L1CAM mutations in three fetuses diagnosed by medical exome sequencing

Taiwan J Obstet Gynecol. 2020 May;59(3):451-455. doi: 10.1016/j.tjog.2020.03.022.

Abstract

Objective: The L1 cell adhesion molecule (L1CAM) gene, encodes the L1 cell adhesion molecule, is involved in the central nervous system development. Its mutations result in L1 syndrome which is associated with brain malformation and nervous developmental delay.

Case report: We presented three fetuses with hydrocephalus and agenesis of the corpus callosum detected by ultrasound, followed by medical exome sequencing (MES) test with L1CAM mutations: two known missense mutation c.551G > A (p. R184Q) and c.1354G > A (p. G452R), and a novel frameshift mutation c.1322delG which causes the early termination of translation (p. G441Afs∗72). By utilizing multiple computational analysis, all the variants were scored to be likely pathogenic.

Conclusion: Combined use of ultrasound and MES to identify the molecular etiology of fetal anomalies may contribute to expanding our knowledge of the clinical phenotype of L1 syndrome observed in the south Chinese population.

Keywords: Congenital hydrocephalus; L1 syndrome; L1CAM; MES; Medical exome sequencing.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Agenesis of Corpus Callosum / diagnosis
  • Agenesis of Corpus Callosum / embryology
  • Agenesis of Corpus Callosum / genetics
  • Exome / genetics*
  • Exome Sequencing*
  • Female
  • Fetus / abnormalities*
  • Genetic Diseases, X-Linked / diagnosis*
  • Genetic Diseases, X-Linked / embryology
  • Genetic Diseases, X-Linked / genetics
  • Humans
  • Hydrocephalus / diagnosis
  • Hydrocephalus / embryology
  • Hydrocephalus / genetics
  • Intellectual Disability / diagnosis*
  • Intellectual Disability / embryology
  • Intellectual Disability / genetics
  • Mutation
  • Neural Cell Adhesion Molecule L1 / genetics*
  • Phenotype
  • Pregnancy
  • Spastic Paraplegia, Hereditary / diagnosis*
  • Spastic Paraplegia, Hereditary / embryology
  • Spastic Paraplegia, Hereditary / genetics
  • Ultrasonography, Prenatal

Substances

  • L1CAM protein, human
  • Neural Cell Adhesion Molecule L1

Supplementary concepts

  • MASA (Mental Retardation, Aphasia, Shuffling Gait, Adducted Thumbs) Syndrome