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

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.