Report of a Novel SHOX Missense Variant in a Boy With Short Stature and His Mother With Leri–Weill Dyschondrosteosis
Heterozygous mutations in the SHOX gene or in the upstream and downstream enhancer elements are associated with 2–22% of cases of idiopathic short stature (OMIM #300582) and with 60% of cases of Leri–Weill dyschondrosteosis (OMIM #127300) with which female subjects are generally more severely affect...
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doaj-eac1f009be71444187ca8bc6af5e903a2020-11-25T02:29:54ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922018-04-01910.3389/fendo.2018.00163342571Report of a Novel SHOX Missense Variant in a Boy With Short Stature and His Mother With Leri–Weill DyschondrosteosisLaura Lucchetti0Paolo Prontera1Amedea Mencarelli2Amedea Mencarelli3Ester Sallicandro4Annalisa Mencarelli5Marta Cofini6Alberto Leonardi7Gabriela Stangoni8Laura Penta9Susanna Esposito10Pediatric Clinic, Department of Surgical and Biomedical Sciences, Università degli Studi di Perugia, Perugia, ItalyMedical Genetics Unit, Santa Maria della Misericordia Hospital, Perugia, ItalyPediatric Clinic, Department of Surgical and Biomedical Sciences, Università degli Studi di Perugia, Perugia, ItalyMedical Genetics Unit, Santa Maria della Misericordia Hospital, Perugia, ItalyMedical Genetics Unit, Santa Maria della Misericordia Hospital, Perugia, ItalyPediatric Clinic, Department of Surgical and Biomedical Sciences, Università degli Studi di Perugia, Perugia, ItalyPediatric Clinic, Department of Surgical and Biomedical Sciences, Università degli Studi di Perugia, Perugia, ItalyPediatric Clinic, Department of Surgical and Biomedical Sciences, Università degli Studi di Perugia, Perugia, ItalyMedical Genetics Unit, Santa Maria della Misericordia Hospital, Perugia, ItalyPediatric Clinic, Department of Surgical and Biomedical Sciences, Università degli Studi di Perugia, Perugia, ItalyPediatric Clinic, Department of Surgical and Biomedical Sciences, Università degli Studi di Perugia, Perugia, ItalyHeterozygous mutations in the SHOX gene or in the upstream and downstream enhancer elements are associated with 2–22% of cases of idiopathic short stature (OMIM #300582) and with 60% of cases of Leri–Weill dyschondrosteosis (OMIM #127300) with which female subjects are generally more severely affected. Approximately 80–90% of SHOX pathogenic variants are deletions or duplications, and the remaining 10–20% are point mutations that primarily give rise to missense variants. The clinical interpretation of novel variants, particularly missense variants, can be challenging and can remain of uncertain significance. Here, we describe a novel missense variant (c.1044 G>T, p.Arg118Met) in a Moroccan boy with a disproportionately short stature and without any radiological traits or bone deformities and in his mother, who had a disproportionately short stature and a Madelung deformity. This variant has not been reported to date in the updated SHOX allelic variant or Human Gene Mutation Databases nor is it listed as a polymorphism in the ExAC browser, dbSNP, or 1000G. This mutation was predicted to be deleterious by three different bioinformatics tools since it modifies an amino acid in a highly conserved DNA-binding domain of the SHOX protein. Based on this evidence, the patient was treated with recombinant human growth hormone.http://journal.frontiersin.org/article/10.3389/fendo.2018.00163/fullshort statureLeri–Weill dyschondrosteosisnovel missense mutationSHOXpediatric endocrinology |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Laura Lucchetti Paolo Prontera Amedea Mencarelli Amedea Mencarelli Ester Sallicandro Annalisa Mencarelli Marta Cofini Alberto Leonardi Gabriela Stangoni Laura Penta Susanna Esposito |
spellingShingle |
Laura Lucchetti Paolo Prontera Amedea Mencarelli Amedea Mencarelli Ester Sallicandro Annalisa Mencarelli Marta Cofini Alberto Leonardi Gabriela Stangoni Laura Penta Susanna Esposito Report of a Novel SHOX Missense Variant in a Boy With Short Stature and His Mother With Leri–Weill Dyschondrosteosis Frontiers in Endocrinology short stature Leri–Weill dyschondrosteosis novel missense mutation SHOX pediatric endocrinology |
author_facet |
Laura Lucchetti Paolo Prontera Amedea Mencarelli Amedea Mencarelli Ester Sallicandro Annalisa Mencarelli Marta Cofini Alberto Leonardi Gabriela Stangoni Laura Penta Susanna Esposito |
author_sort |
Laura Lucchetti |
title |
Report of a Novel SHOX Missense Variant in a Boy With Short Stature and His Mother With Leri–Weill Dyschondrosteosis |
title_short |
Report of a Novel SHOX Missense Variant in a Boy With Short Stature and His Mother With Leri–Weill Dyschondrosteosis |
title_full |
Report of a Novel SHOX Missense Variant in a Boy With Short Stature and His Mother With Leri–Weill Dyschondrosteosis |
title_fullStr |
Report of a Novel SHOX Missense Variant in a Boy With Short Stature and His Mother With Leri–Weill Dyschondrosteosis |
title_full_unstemmed |
Report of a Novel SHOX Missense Variant in a Boy With Short Stature and His Mother With Leri–Weill Dyschondrosteosis |
title_sort |
report of a novel shox missense variant in a boy with short stature and his mother with leri–weill dyschondrosteosis |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Endocrinology |
issn |
1664-2392 |
publishDate |
2018-04-01 |
description |
Heterozygous mutations in the SHOX gene or in the upstream and downstream enhancer elements are associated with 2–22% of cases of idiopathic short stature (OMIM #300582) and with 60% of cases of Leri–Weill dyschondrosteosis (OMIM #127300) with which female subjects are generally more severely affected. Approximately 80–90% of SHOX pathogenic variants are deletions or duplications, and the remaining 10–20% are point mutations that primarily give rise to missense variants. The clinical interpretation of novel variants, particularly missense variants, can be challenging and can remain of uncertain significance. Here, we describe a novel missense variant (c.1044 G>T, p.Arg118Met) in a Moroccan boy with a disproportionately short stature and without any radiological traits or bone deformities and in his mother, who had a disproportionately short stature and a Madelung deformity. This variant has not been reported to date in the updated SHOX allelic variant or Human Gene Mutation Databases nor is it listed as a polymorphism in the ExAC browser, dbSNP, or 1000G. This mutation was predicted to be deleterious by three different bioinformatics tools since it modifies an amino acid in a highly conserved DNA-binding domain of the SHOX protein. Based on this evidence, the patient was treated with recombinant human growth hormone. |
topic |
short stature Leri–Weill dyschondrosteosis novel missense mutation SHOX pediatric endocrinology |
url |
http://journal.frontiersin.org/article/10.3389/fendo.2018.00163/full |
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