Novel GPC3 Gene Mutation in Simpson-Golabi-Behmel Syndrome with Endocrine Anomalies: A Case Report

Abstract

Simpson-Golabi-Behmel syndrome (SGBS) represents a rare X-linked recessive syndrome with prenatal and postnatal overgrowth, coarse facial features, congenital malformations, organomegaly and an increased risk of tumors. Mutations on the GPC3 gene, encoding the glypican-3 protein, have previously been shown to cause the disease. In this report, a 12-year-old Chinese boy was hospitalized in our institution for some clinical features of SGBS. His serum endocrine evaluation showed hormone level abnormalities, including high prolactin, high testosterone, high thyroid-stimulating hormone (TSH) levels, and low estradiol levels. Whole exome sequencing (WES) was performed in the patient for mutation analysis and a novel hemizygous mutation, c.185delT, p.(Leu62Cysfs*22), on the GPC3 gene, was identified. The mother was a heterozygous carrier. The SGBS patients might present with endocrine anomalies, which adds to the clinical heterogeneity of the disease. The novel GPC3 mutation c.185delT expands the mutational spectrum of the GPC3 gene.

Overgrowth syndromes, diagnosis and management

“…The remaining overgrowth syndromes do not cluster as linearly; however, they do highlight some important biological processes. For example, the DICER1 syndrome and GLOW syndrome implicate microRNA regulation in growth regulation and Simpson–Golabi–Behmel syndrome ties GPC3 into controlling human linear growth through an unknown mechanism [8,28 ▪▪ ].…”

“…For instance, Proteus syndrome arises from somatic activating mutations in the AKT1 gene, while Sotos syndrome results from inactivating mutations or copy number losses of the NSD1 gene. Molecular testing has not only verified diagnoses but also expanded the clinical phenotypes to encompass atypical cases, often with distinct molecular mechanisms [8,9].…”