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Reporting a novel growth hormone receptor gene variant in an Iranian consanguineous pedigree with Laron syndrome: a case report

BACKGROUND: Human growth hormone (hGH) plays a crucial role in growth by binding to growth hormone receptor (GHR) in target cells. Binding of GH molecules to their cognate receptors triggers downstream signaling pathways leading to the transcription of several genes, including insulin-like growth fa...

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Autores principales: Bitarafan, Fatemeh, Khodaeian, Mehrnoosh, Garrousi, Fatemeh, Khalesi, Raziyeh, Ghazi Nader, Donya, Karimi, Behnam, Alibakhshi, Reza, Garshasbi, Masoud
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10357607/
https://www.ncbi.nlm.nih.gov/pubmed/37474955
http://dx.doi.org/10.1186/s12902-023-01388-1
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author Bitarafan, Fatemeh
Khodaeian, Mehrnoosh
Garrousi, Fatemeh
Khalesi, Raziyeh
Ghazi Nader, Donya
Karimi, Behnam
Alibakhshi, Reza
Garshasbi, Masoud
author_facet Bitarafan, Fatemeh
Khodaeian, Mehrnoosh
Garrousi, Fatemeh
Khalesi, Raziyeh
Ghazi Nader, Donya
Karimi, Behnam
Alibakhshi, Reza
Garshasbi, Masoud
author_sort Bitarafan, Fatemeh
collection PubMed
description BACKGROUND: Human growth hormone (hGH) plays a crucial role in growth by binding to growth hormone receptor (GHR) in target cells. Binding of GH molecules to their cognate receptors triggers downstream signaling pathways leading to the transcription of several genes, including insulin-like growth factor (IGF)-1. Pathogenic variants in the GHR gene can result in structural and functional defects in the GHR protein, leading to Laron Syndrome (LS) with the primary clinical manifestation of short stature. So far, around 100 GHR variants have been reported, mostly biallelic, as causing LS. CASE PRESENTATION: We report on three siblings from an Iranian consanguineous family who presented with dwarfism. Whole-exome sequencing (WES) was performed on the proband, revealing a novel homozygous missense variant in the GHR gene (NM_000163.5; c.610 T > A, p.(Trp204Arg)) classified as a likely pathogenic variant according to the recommendation of the American College of Medical Genetics (ACMG). Co-segregation analysis was investigated using Sanger sequencing. CONCLUSIONS: To date, approximately 400–500 LS cases with GHR biallelic variants, out of them 10 patients originating from Iran, have been described in the literature. Given the high rate of consanguineous marriages in the Iranian population, the frequency of LS is expected to be higher, which might be explained by undiagnosed cases. Early diagnosis of LS is very important, as treatment is available for this condition. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12902-023-01388-1.
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spelling pubmed-103576072023-07-21 Reporting a novel growth hormone receptor gene variant in an Iranian consanguineous pedigree with Laron syndrome: a case report Bitarafan, Fatemeh Khodaeian, Mehrnoosh Garrousi, Fatemeh Khalesi, Raziyeh Ghazi Nader, Donya Karimi, Behnam Alibakhshi, Reza Garshasbi, Masoud BMC Endocr Disord Case Report BACKGROUND: Human growth hormone (hGH) plays a crucial role in growth by binding to growth hormone receptor (GHR) in target cells. Binding of GH molecules to their cognate receptors triggers downstream signaling pathways leading to the transcription of several genes, including insulin-like growth factor (IGF)-1. Pathogenic variants in the GHR gene can result in structural and functional defects in the GHR protein, leading to Laron Syndrome (LS) with the primary clinical manifestation of short stature. So far, around 100 GHR variants have been reported, mostly biallelic, as causing LS. CASE PRESENTATION: We report on three siblings from an Iranian consanguineous family who presented with dwarfism. Whole-exome sequencing (WES) was performed on the proband, revealing a novel homozygous missense variant in the GHR gene (NM_000163.5; c.610 T > A, p.(Trp204Arg)) classified as a likely pathogenic variant according to the recommendation of the American College of Medical Genetics (ACMG). Co-segregation analysis was investigated using Sanger sequencing. CONCLUSIONS: To date, approximately 400–500 LS cases with GHR biallelic variants, out of them 10 patients originating from Iran, have been described in the literature. Given the high rate of consanguineous marriages in the Iranian population, the frequency of LS is expected to be higher, which might be explained by undiagnosed cases. Early diagnosis of LS is very important, as treatment is available for this condition. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12902-023-01388-1. BioMed Central 2023-07-20 /pmc/articles/PMC10357607/ /pubmed/37474955 http://dx.doi.org/10.1186/s12902-023-01388-1 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Case Report
Bitarafan, Fatemeh
Khodaeian, Mehrnoosh
Garrousi, Fatemeh
Khalesi, Raziyeh
Ghazi Nader, Donya
Karimi, Behnam
Alibakhshi, Reza
Garshasbi, Masoud
Reporting a novel growth hormone receptor gene variant in an Iranian consanguineous pedigree with Laron syndrome: a case report
title Reporting a novel growth hormone receptor gene variant in an Iranian consanguineous pedigree with Laron syndrome: a case report
title_full Reporting a novel growth hormone receptor gene variant in an Iranian consanguineous pedigree with Laron syndrome: a case report
title_fullStr Reporting a novel growth hormone receptor gene variant in an Iranian consanguineous pedigree with Laron syndrome: a case report
title_full_unstemmed Reporting a novel growth hormone receptor gene variant in an Iranian consanguineous pedigree with Laron syndrome: a case report
title_short Reporting a novel growth hormone receptor gene variant in an Iranian consanguineous pedigree with Laron syndrome: a case report
title_sort reporting a novel growth hormone receptor gene variant in an iranian consanguineous pedigree with laron syndrome: a case report
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10357607/
https://www.ncbi.nlm.nih.gov/pubmed/37474955
http://dx.doi.org/10.1186/s12902-023-01388-1
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