A case report and literature review of monoallelic mutation of GHR

Marie Mitani, Hirohito Shima, Takeshi Sato, Tomohiro Inoguchi, Tsutomu Kamimaki, Maki Fukami, Tomonobu Hasegawa

Research output: Contribution to journalArticle

Abstract

Monoallelic mutations of GHR have been described in idiopathic short stature (ISS), although the significance of these remain unclear. We report a case of ISS with novel monoallelic S219L mutation of GHR and discuss the possible significance of monoallelic GHR mutation in ISS. The proband, a 13.9-year-old Japanese boy, had severe short stature (-3.8 standard deviation [SD]). Serum insulin-like growth factor (IGF)-I level and growth hormone (GH) secretion was normal. His parents were nonconsanguineous and had normal stature. Genetic analyses revealed a novel monoallelic missense variation in exon 7 of GHR (S219L). The proband's mother had the same variation. S219L might be the novel mutation judging from there being no registration of it as a single-nucleotide polymorphism (SNP) in any database, evolutional conservation of Ser 219 , in silico analyses, and computational molecular visualization analysis. Furthermore, a review of the literature showed that the median height of missense mutation carriers of GHR was relatively low. We propose the possibility that monoallelic mutation of GHR increases the susceptibility to short stature.

Original languageEnglish
JournalJournal of Pediatric Endocrinology and Metabolism
DOIs
Publication statusPublished - 2019 Jan 1

Fingerprint

Mutation
Missense Mutation
Insulin-Like Growth Factor I
Computer Simulation
Growth Hormone
Single Nucleotide Polymorphism
Exons
Parents
Mothers
Databases
Serum

Keywords

  • GH insensitivity
  • GH receptor
  • idiopathic short stature

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

A case report and literature review of monoallelic mutation of GHR. / Mitani, Marie; Shima, Hirohito; Sato, Takeshi; Inoguchi, Tomohiro; Kamimaki, Tsutomu; Fukami, Maki; Hasegawa, Tomonobu.

In: Journal of Pediatric Endocrinology and Metabolism, 01.01.2019.

Research output: Contribution to journalArticle

Mitani, Marie ; Shima, Hirohito ; Sato, Takeshi ; Inoguchi, Tomohiro ; Kamimaki, Tsutomu ; Fukami, Maki ; Hasegawa, Tomonobu. / A case report and literature review of monoallelic mutation of GHR. In: Journal of Pediatric Endocrinology and Metabolism. 2019.
@article{e59e07a4201e48d6a1024e20e8692cd2,
title = "A case report and literature review of monoallelic mutation of GHR",
abstract = "Monoallelic mutations of GHR have been described in idiopathic short stature (ISS), although the significance of these remain unclear. We report a case of ISS with novel monoallelic S219L mutation of GHR and discuss the possible significance of monoallelic GHR mutation in ISS. The proband, a 13.9-year-old Japanese boy, had severe short stature (-3.8 standard deviation [SD]). Serum insulin-like growth factor (IGF)-I level and growth hormone (GH) secretion was normal. His parents were nonconsanguineous and had normal stature. Genetic analyses revealed a novel monoallelic missense variation in exon 7 of GHR (S219L). The proband's mother had the same variation. S219L might be the novel mutation judging from there being no registration of it as a single-nucleotide polymorphism (SNP) in any database, evolutional conservation of Ser 219 , in silico analyses, and computational molecular visualization analysis. Furthermore, a review of the literature showed that the median height of missense mutation carriers of GHR was relatively low. We propose the possibility that monoallelic mutation of GHR increases the susceptibility to short stature.",
keywords = "GH insensitivity, GH receptor, idiopathic short stature",
author = "Marie Mitani and Hirohito Shima and Takeshi Sato and Tomohiro Inoguchi and Tsutomu Kamimaki and Maki Fukami and Tomonobu Hasegawa",
year = "2019",
month = "1",
day = "1",
doi = "10.1515/jpem-2018-0365",
language = "English",
journal = "Journal of Pediatric Endocrinology and Metabolism",
issn = "0334-018X",
publisher = "Walter de Gruyter GmbH & Co. KG",

}

TY - JOUR

T1 - A case report and literature review of monoallelic mutation of GHR

AU - Mitani, Marie

AU - Shima, Hirohito

AU - Sato, Takeshi

AU - Inoguchi, Tomohiro

AU - Kamimaki, Tsutomu

AU - Fukami, Maki

AU - Hasegawa, Tomonobu

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Monoallelic mutations of GHR have been described in idiopathic short stature (ISS), although the significance of these remain unclear. We report a case of ISS with novel monoallelic S219L mutation of GHR and discuss the possible significance of monoallelic GHR mutation in ISS. The proband, a 13.9-year-old Japanese boy, had severe short stature (-3.8 standard deviation [SD]). Serum insulin-like growth factor (IGF)-I level and growth hormone (GH) secretion was normal. His parents were nonconsanguineous and had normal stature. Genetic analyses revealed a novel monoallelic missense variation in exon 7 of GHR (S219L). The proband's mother had the same variation. S219L might be the novel mutation judging from there being no registration of it as a single-nucleotide polymorphism (SNP) in any database, evolutional conservation of Ser 219 , in silico analyses, and computational molecular visualization analysis. Furthermore, a review of the literature showed that the median height of missense mutation carriers of GHR was relatively low. We propose the possibility that monoallelic mutation of GHR increases the susceptibility to short stature.

AB - Monoallelic mutations of GHR have been described in idiopathic short stature (ISS), although the significance of these remain unclear. We report a case of ISS with novel monoallelic S219L mutation of GHR and discuss the possible significance of monoallelic GHR mutation in ISS. The proband, a 13.9-year-old Japanese boy, had severe short stature (-3.8 standard deviation [SD]). Serum insulin-like growth factor (IGF)-I level and growth hormone (GH) secretion was normal. His parents were nonconsanguineous and had normal stature. Genetic analyses revealed a novel monoallelic missense variation in exon 7 of GHR (S219L). The proband's mother had the same variation. S219L might be the novel mutation judging from there being no registration of it as a single-nucleotide polymorphism (SNP) in any database, evolutional conservation of Ser 219 , in silico analyses, and computational molecular visualization analysis. Furthermore, a review of the literature showed that the median height of missense mutation carriers of GHR was relatively low. We propose the possibility that monoallelic mutation of GHR increases the susceptibility to short stature.

KW - GH insensitivity

KW - GH receptor

KW - idiopathic short stature

UR - http://www.scopus.com/inward/record.url?scp=85063499797&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85063499797&partnerID=8YFLogxK

U2 - 10.1515/jpem-2018-0365

DO - 10.1515/jpem-2018-0365

M3 - Article

JO - Journal of Pediatric Endocrinology and Metabolism

JF - Journal of Pediatric Endocrinology and Metabolism

SN - 0334-018X

ER -