Partial growth-hormone insensitivity: The role of growth-hormone receptor mutations in idiopathic short stature

Goddard, Audrey D.; Dowd, Patrick J.; Chernausek, Steven D.; Geffner, Mitchell E.; Gertner, Joseph M.; Hintz, Raymond L.; Hopwood, Nancy J.; Kaplan, Selna L.; Plotnick, Leslie P.; Rogol, Alan D.; Rosenfield, Robert L.; Saenger, Paul; Mauras, Nellie; Hershkopf, Richard; Angulo, Morris; Attie, Kenneth M.

doi:10.1016/s0022-3476(97)70012-x

Cited by 101 publications

(84 citation statements)

References 13 publications

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“…Several abnormal forms of the GHR have been identified, which result in abnormal GH binding, defective receptor dimerization, and defective signal transduction (17). However, it is uncertain whether heterozygous mutations in GHR play a major role in determining growth (18,19).…”

Section: Discussionmentioning

confidence: 99%

Heterozygous GHR gene mutation in a child with idiopathic short stature

Pagani

Petkovic

Messini³

et al. 2014

Journal of Pediatric Endocrinology and Metabolism

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Several monogenic defects have been reported to be associated with idiopathic short stature. Focusing on growth hormone receptor (GHR)-gene alterations, the heterozygosity of the same gene defect may be associated with a range of growth deficits. We found a heterozygous mutation (V144I) within exon 6 of the GHR gene in a patient with a low level of insulin-like growth factor I (IGF-I), normal level of GH, and severe short stature. Despite the lack of statistical difference, an overall tendency for reduced wt-GH-induction of GHR activation and Jak/Stat signalling in cells transiently expressing GHR-V144I alone or co-expressing wt-GHR compared to cells expressing only wt-GHR was found when GH doses were increased. Our results suggest that, although GHR sequence variants are responsible for some functional alterations commonly observed in children with idiopathic short stature, these changes may not explain all the height deficits observed in these subjects.

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Section: Discussionmentioning

confidence: 99%

Heterozygous GHR gene mutation in a child with idiopathic short stature

Pagani

Petkovic

Messini³

et al. 2014

Journal of Pediatric Endocrinology and Metabolism

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“…There are several reports presenting data on heterozygous GHR gene defects possibly leading to short stature [30][31][32][33]. Defects in the GHR gene were present at a modest frequency (approx.…”

Section: Heterozygosities For Ghr Mutationsmentioning

confidence: 99%

Biological Determinants of Responsiveness to Growth Hormone: Pharmacogenomics and Personalized Medicine

Mullis¹

2010

Current Indications for Growth Hormone Therapy

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It is becoming most clear that many genes are involved in controlling the regulation of growth. Ultimately however, at the level of growth hormone (GH), the relevant question may be not whether a patient is GH-deficient, but whether he is GH-responsive. As these disturbances can be divided into two gross categories, namely alterations causing subnormal GH secretion and/or those presenting with subnormal GH sensitivity/responsiveness, the main aim of this review is to focus on genes involved in growth regulation leading to short stature caused by an alteration of GH insensitivity/GH responsiveness; in other words, clinical circumstances where individually adapted GH replacement therapy may help to increase height velocity and eventually final height.

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“…descreveram pela primeira vez a presença de mutações no gene GHR em crianças com baixa estatura idiopática que apresentavam níveis baixos de IGF-I e de sua proteína carreadora (GHBP) (85). Outras publicações se seguiram e atualmente há 8 mutações descritas como responsáveis pela insensibilidade parcial ao GH com uma freqüência entre 3 a 5% em crianças com baixa estatura idiopática (82,(85)(86)(87)(88). Em nosso grupo encontramos 2 mutações em heterozigose em 47 crianças (4,2%) com baixa estatura idiopática selecionadas por apresentarem níveis de IGF-I e/ou IGFBP-3 ≤ -1 DP para idade e sexo (89).…”

Section: Insensibilidade Ao Hormônio De Crescimento Ghr (Receptor De Gh)unclassified

Bases Genéticas dos Distúrbios de Crescimento

Marui

Souza

Carvalho

et al. 2002

Arq Bras Endocrinol Metab

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A integridade do eixo GHRH-GH-IGF-I é fundamental para o crescimento normal de um indivíduo. Mutações nos genes responsáveis por cada uma das etapas deste eixo resultam em baixa estatura grave. Podemos dividir os distúrbios de crescimento em: 1. Deficiência de GH associada a deficiências de outros hormônios hipofisários por alterações em fatores de transcrição envolvidos na organogênese hipofisária (HESX1/RPX, LHX3 e LHX4, PROP-1, PIT-1); 2. Deficiência isolada de GH (receptor do GHRH:GHRHR, GH-1, GH bioinativo); e 3. Insensibilidade ao GH (receptor de GH:GHR, gene da IGF-I e receptor da IGF-I:IGFR). Serão discutidos também os genes implicados na baixa estatura da Síndrome de Turner (SHOX) e Síndrome de Noonan (PTPN11). Atualmente estamos analisando no Laboratório de Hormônios e Genética Molecular da Disciplina de Endocrinologia da FMUSP - LIM 42 os genes HESX-1, LHX3, LHX4, PROP-1, GHRHR, GH-1, GHR, SHOX e PTPN11 em pacientes com baixa estatura e características clínicas e laboratoriais que sugerem o envolvimento destes genes.

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Partial growth-hormone insensitivity: The role of growth-hormone receptor mutations in idiopathic short stature

Cited by 101 publications

References 13 publications

Heterozygous GHR gene mutation in a child with idiopathic short stature

Heterozygous GHR gene mutation in a child with idiopathic short stature

Biological Determinants of Responsiveness to Growth Hormone: Pharmacogenomics and Personalized Medicine

Bases Genéticas dos Distúrbios de Crescimento

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