Whole exome sequencing aids the diagnosis of Simpson-Golabi-Behmel syndrome in two male fetuses

J Int Med Res. 2020 Jan;48(1):300060519859752. doi: 10.1177/0300060519859752. Epub 2019 Jul 15.

Abstract

Objective: To diagnose and explore the genetic aetiology of Simpson–Golabi–Behmel syndrome type 1 (SGBS1) in two male fetuses.

Methods: Prenatal ultrasound scans and further genetic analysis using karyotype analysis, chromosomal microarray analysis, whole exome sequencing (WES) and Sanger sequencing were conducted.

Results: Prenatal ultrasound scans of two fetuses showed multiple congenital anomalies and hydramnios. Subsequent to termination of the pregnancies, a novel nonsense variant (c.892G>T, p.E298*) in the glypican 3 (GPC3) gene of the two fetuses was identified by WES and further confirmed by Sanger sequencing. The two fetuses were diagnosed with SGBS1. The mother was heterozygous for the c.892G>T variant.

Conclusion: This study describes the prenatal sonographic features of SGBS1, emphasizes the role of WES in the diagnosis of SGBS1 and expands the known mutation spectrum of the GPC3 gene.

Keywords: GPC3; Simpson–Golabi–Behmel syndrome type 1; fetal ultrasound findings; whole exome sequencing.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Arrhythmias, Cardiac / diagnosis*
  • Arrhythmias, Cardiac / genetics*
  • Base Sequence
  • Exome Sequencing*
  • Family
  • Female
  • Fetus / abnormalities
  • Fetus / pathology*
  • Genetic Diseases, X-Linked / diagnosis*
  • Genetic Diseases, X-Linked / genetics*
  • Gigantism / diagnosis*
  • Gigantism / genetics*
  • Heart Defects, Congenital / diagnosis*
  • Heart Defects, Congenital / genetics*
  • Humans
  • Intellectual Disability / diagnosis*
  • Intellectual Disability / genetics*
  • Male
  • Pedigree

Supplementary concepts

  • Simpson-Golabi-Behmel syndrome