A patient with a unique frameshift mutation in <i>GPC3</i>, causing Simpson–Golabi–Behmel syndrome, presenting with craniosynostosis, penoscrotal hypospadias, and a large prostatic utricle

Villarreal, Diana; Villarreal, Humberto; Paez, Ana; Peppas, Dennis S.; Lynch, Jane; Roeder, Elizabeth; Powers, George

doi:10.1002/ajmg.a.36086

Cited by 13 publications

(8 citation statements)

References 35 publications

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“…The patient's condition was consistent with typical clinical manifestations of SGBS1, such as postnatal macrosomia, coarse facial features, macrostomia, macroglossia, and polydactyly. [8] The clinical phenotype also included subclinical hypothyroidism, which has not been reported in other case reports or literature related to SGBS1. Subclinical hypothyroidism refers to that serum TSH is above the upper limit of normal range, while free T4 is normal.…”

Section: Discussionmentioning

confidence: 96%

Simpson−Golabi−Behmel syndrome type 1 with subclinical hypothyroidism

Zhang

et al. 2019

Medicine

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Rationale:Simpson−Golabi−Behmel syndrome type 1 (SGBS1) is caused by mutations in GPC3 or in both GPC3 and GPC4. Physical manifestations of SGBS1 include fetal overgrowth and macrostomia, macroglossia. Subclinical hypothyroidism has never been reported in SGBS1 cases.Patient concerns:An 8-days-old boy was referred to our hospital with persistent hypoglycemia and special facies. And the infant showed elevated levels of thyroid-stimulating hormone (TSH). Free T4 and free T3 were normal.Diagnoses:Definitive diagnosis of SGBS1 depends on clinical features and genetic testing. A nonsense mutation (c.1515C > A, p. Cys505∗) was tested by whole-exome sequencing.Interventions:Normal blood glucose levels were maintained with glucose infusions. Levothyroxine was given to the patient for treating subclinical hypothyroidism.Outcomes:The parents decided to abandon the treatment of the patient. We learned that the patient died of a lung infection by a telephone follow-up.Lessons:Subclinical hypothyroidism could be added to the known clinical manifestations of SGBS1.

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Section: Discussionmentioning

confidence: 96%

Simpson−Golabi−Behmel syndrome type 1 with subclinical hypothyroidism

Zhang

et al. 2019

Medicine

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“…Table details GPC3 mutations published between March 1996 and December 2017 in the international peer‐reviewed literature (PubMed database) and The Human Gene Mutation Database (HGMD professional 2016.4) following HGVS nomenclature guidelines (http://www.HGVS.org) and the reference sequence GenBank entry NM_004484.3. We collected 57 distinct GPC3 mutations detected in 71 unrelated families (Agatep et al., ; Das Bhowmik & Dalal, ; Day & Fryer, ; DiMaio, Yang, Mahoney, McGrath, & Li, ; Ganesamoorthy et al., ; Garavelli et al., ; Gertsch, Kirmani, Ackerman, & Babovic‐Vuksanovic, ; Gurrieri et al., ; Halayem et al., ; Hughes‐Benzie et al., ; Kehrer et al., ; Kosaki et al., ; Li et al., ; Lindsay et al., ; Magini et al., ; Mariani et al., ; Mateos et al., ; Mujezinović et al., ; Ochiai et al., ; Okamoto, Yagi, Imura, & Wada, ; Pilia et al., ; Rodríguez‐Criado et al., ; Romanelli et al., ; Sakazume et al., ; Schmidt, Hollstein, Kaiser, & Gillessen‐Kaesbach, ; Shimojima et al., ; Spencer, Fieggen, Vorster, & Beighton, ; Støve et al., ; Thomas et al., ; Vaisfeld, Pomponi, Pietrobono, Tabolacci, & Neri, ; Veugelers et al., , ; Villarreal et al., ; Weichert et al., ; Xuan, Hughes‐Benzie, & MacKenzie, ; Yano et al., ; Young, Wishnow, & Nigro, ). In this study, we also report 38 GPC3 mutations in 63 additional male patients from 49 unrelated families (Cf.…”

Section: Mutational Spectrummentioning

confidence: 99%

Mutation update for theGPC3gene involved in Simpson-Golabi-Behmel syndrome and review of the literature

et al. 2018

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Simpson-Golabi-Behmel syndrome (SGBS) is an X-linked multiple congenital anomalies and overgrowth syndrome caused by a defect in the glypican-3 gene (GPC3). Until now, GPC3 mutations have been reported in isolated cases or small series and the global genotypic spectrum of these mutations has never been delineated. In this study, we review the 57 previously described GPC3 mutations and significantly expand this mutational spectrum with the description of 29 novel mutations. Compiling our data and those of the literature, we provide an overview of 86 distinct GPC3 mutations identified in 120 unrelated families, ranging from single nucleotide variations to complex genomic rearrangements and dispersed throughout the entire coding region of GPC3. The vast majority of them are deletions or truncating mutations (frameshift, nonsense mutations) predicted to result in a loss-of-function. Missense mutations are rare and the two which were functionally characterized, impaired GPC3 function by preventing GPC3 cleavage and cell surface addressing respectively. This report by describing for the first time the wide mutational spectrum of GPC3 could help clinicians and geneticists in interpreting GPC3 variants identified incidentally by high-throughput sequencing technologies and also reinforces the need for functional validation of non-truncating mutations (missense, in frame mutations, duplications).

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“…[14][15][16][17][18][19][20][21][22] Overgrowth Syndrome caused by mutations in glypican 3 (GPC3) gene is localized on Xq26.1 [23,24] which encrypts glypican-3. [17,19,20,[25][26][27][28][29] that seemingly acting a bad part in growth control by an anonymous fate, However, outcomes from an exhaustive qualified study of growth forms in dual mutants missing GPC3 provided conclusive genetic evidence inconsistent with the theory that GPC3 performances as a growth suppressor. [29] Such a proteoglycan is contingent to show a vital part in regulate and diagnosis in mesodermal tissues and ISSN: 2456-7132 Available online at Journals.aijr.in Simpson-Golabi-Behmel Syndrome (SGBS) in tumors predisposition.…”

Section: Introductionmentioning

confidence: 94%

Identification of Novel Key Biomarkers in Simpson-Golabi-Behmel Syndrome (SGBS): Evidence from Bioinformatics Analysis

Mustafa¹,

Abdelmoneim²,

Elfadol³

et al. 2019

Int. Ann. Sci.

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The Simpson-Golabi-Behmel Syndrome (SGBS) or overgrowth Syndrome is an uncommon genetic X-linked disorder highlighted by macrosomia, renal defects, cardiac weaknesses and skeletal abnormalities. The purpose of the work was to classify the functional nsSNPs of GPC3 to serve as genetic biomarkers for overgrowth syndrome. The raw data of GPC3 gene were retrieved from dbSNP database and used to examine the most damaging effect using eight functional analysis tools, while we used I-mutant and MUPro to examine the effect of SNPs on GPC3 protein structure; The 3D structure of GPC3 protein is not found in the PDB, so RaptorX was used to create a 3D structural prototype to visualize the amino acids alterations by UCSF Chimera; For biophysical validation we used project HOPE; Lastly we run conservational analysis by BioEdit and Consurf web server respectively. Our results revealed three novel missense mutations (rs1460413167, rs1295603457 and rs757475450) that are that are more likely to be responsible for disturbance in the function and structure of GPC3. This work provides new insight into the molecular basis of overgrowth Syndrome by evidence from bioinformatics analysis. Three novel missense mutations (rs757475450, rs1295603457 and rs1460413167) are more likely to be responsible for disturbance in the function and structure of GPC3; therefore, they may be assisting as genetic biomarkers for overgrowth syndrome. As well as these SNPs can be used for the larger population-based studies of overgrowth syndrome.

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A patient with a unique frameshift mutation in GPC3, causing Simpson–Golabi–Behmel syndrome, presenting with craniosynostosis, penoscrotal hypospadias, and a large prostatic utricle

Cited by 13 publications

References 35 publications

Simpson−Golabi−Behmel syndrome type 1 with subclinical hypothyroidism

Simpson−Golabi−Behmel syndrome type 1 with subclinical hypothyroidism

Mutation update for theGPC3gene involved in Simpson-Golabi-Behmel syndrome and review of the literature

Identification of Novel Key Biomarkers in Simpson-Golabi-Behmel Syndrome (SGBS): Evidence from Bioinformatics Analysis

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