Prenatal case of Simpson–Golabi–Behmel syndrome with a de novo 370Kb‐sized microdeletion of Xq26.2 compassing partial GPC3 gene and review

Abstract

Background Simpson–Golabi–Behmel syndrome type 1 (SGBS1) is a rare X‐linked recessive disorder characterized by pre‐ and postnatal overgrowth and a broad spectrum of anomalies including craniofacial dysmorphism, heart defects, renal, and genital anomalies. Due to the ultrasound findings are not pathognomonic for this syndrome, most clinical diagnosis of SGBS1 are made postnatally. Methods A pregnant woman with abnormal prenatal sonographic findings was advised to perform molecular diagnosis. Single nucleotide polymorphism array (SNP array) was performed in the fetus, and the result was validated with multiplex ligation‐dependent probe amplification (MLPA) and real‐time quantitative PCR (qPCR). Results The prenatal sonographic presented with increased nuchal translucency at 13 gestational weeks, and later at 21 weeks with cleft lip and palate, heart defect, increased amniotic fluid index and over growth. A de novo 370Kb‐deletion covering the 5′‐UTR and exon 1 of GPC3 gene was detected in the fetus by SNP array, which was subsequently confirmed by MLPA and qPCR. Conclusion The de novo 370Kb hemizygous deletion of 5′‐UTR and exon 1 of GPC3 results in the SGBS1 of this Chinese family. Combination of ultrasound and genetics tests helped us effectively to diagnose the prenatal cases of SGBS1. Our findings also enlarge the spectrum of mutations in GPC3 gene.

A rare case of family suffering from Simpson-Golabi-Behmel syndrome with an uncommon manifestation in a mother and 2 sons

“…It made it the second most frequent mutation causing SGBS type I after c.256C > T, p.(Arg86*), which was detected in 7 families [2]. Other types of mutations responsible for SGBS type I include large deletions, large duplications, frameshift indels, other types of nonsense mutations, [16]. Also, Chong et al described a similar case in which an ultrasound examination performed at the 30 th week of gestation revealed many pathological changes, including a left-sided cleft [17].…”

Maternal body fluid lncRNAs serve as biomarkers to diagnose ventricular septal defect: from amniotic fluid to plasma

“…KATNB1 is a critical regulator of heart development, and mutations in KATNB1 will cause heart left-right asymmetry defects (Furtado et al, 2017). GPC3 is widely expressed in embryonic mesodermal tissues and plays an important role in regulating cell proliferation and apoptosis in the embryonic heart (Liu et al, 2021). IDS contributes to cardiomyocyte differentiation disorder and aberrant heart development by affecting the catabolism of GAGs (Matsuhisa and Imaizumi, 2021).…”

A prenatal case of Simpson-Golabi-Behmel syndrome type 1 with a 0.26-Mb deletion fragment at Xq26.2 inherited from mother

“…Simpson-Golabi-Behmel syndrome type 1 (SGBS1, OMIM 312870) is an X-linked recessive disorder with the typical features of SGBS1 including pre/postnatal overgrowth, multi-system abnormalities such as cardiovascular defects, abnormal craniofacial features, genitourinary defects, and skeletal anomalies, as well as increased risks for embryonal tumors. [ 1 , 2 ] It is the common one of the two subtypes associated with mutations of glypican-3 (GPC3) and glypican-4 (GPC4), [ 3 ] which is usually diagnosed postnatally. Recently, sequencing technology has been widely applied to prenatal diagnosis and helped clinicians further define the genetic diagnosis associated with fetal structural abnormalities.…”