Mutations of the Growth Hormone Receptor in Children with Idiopathic Short Stature

Goddard, Audrey D.; Covello, Robin; Luoh, Shiuh-Ming; Clackson, Tim; Attie, Kenneth M.; Gesundheit, Neil; Rundle, Amy Chen; Wells, James A.; Carlsson, Lena

doi:10.1056/nejm199510263331701

Cited by 272 publications

(143 citation statements)

References 27 publications

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“…Thus we could not analyze genes of her family members. Recently, GHR mutations were identified among'children with idiopathic short stature (Goddard et al, 1995). We suppose that the GHR mutation may not be race-or family-specific and it would be detected in Japanese patients with Laron syndrome or other type of growth deficiency.…”

Section: Discussionmentioning

confidence: 96%

The growth hormone receptor gene mutation of a japanese patient with laron syndrome

et al. 1997

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SummaryDeletions and point mutations of the growth hormone (GH) receptor gene (GHR) have been identified in patients with Laron syndrome. We report the first detection of the GHR mutation among Japanese patients with Laron syndrome. Using the Japanese female patient's genomic DNA as a template, all exons and flanking portions of introns of GHR were amplified by polymerase chain reaction (PCR). Sequencing of the PCR products showed that the patient was homozygous for a G to A substitution at the first position of intron 4. This substitution was same as that detected in a Spanish patient and a north European patient. The base change occurred at the 5' splice consensus sequence of intron 4, resulting in the abolition of a BanI restriction site. Since this substitution was not detected by a BanI restriction analysis in 85 control individuals, it is more likely a disease-related splice mutation than a polymorphism. The mutation in our patient was predicted to destroy the original 5" splice site of intron 4 of GHR and to produce a new cryptic splice site, leading to abnormal mRNA processing and a lack of GH binding activity of GH-binding protein (GHBP).

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Section: Discussionmentioning

confidence: 96%

The growth hormone receptor gene mutation of a japanese patient with laron syndrome

et al. 1997

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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%

“…A polymorphism is defined as a DNA sequence variant that occurs in at least 1% of the population [36]. Polymorphisms of the GHR gene have been reported in the general population and have been described in exons 3, 6 and 10 [31]. While the latter two are classical single nucleotide polymorphisms, the polymorphism in exon 3 is an unusual one, leading to retention (full-length, fl; GHRfl) or deletion of exon 3 (d3; GHRd3), which encodes a 22-amino-acid residue sequence in the extracellular domain [37,38].…”

Section: Polymorphism Of the Ghrmentioning

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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Mutations of the Growth Hormone Receptor in Children with Idiopathic Short Stature

Abstract: Some children with idiopathic short stature may have partial insensitivity to GH due to mutations in the GH-receptor gene.

Cited by 272 publications

References 27 publications

The growth hormone receptor gene mutation of a japanese patient with laron syndrome

The growth hormone receptor gene mutation of a japanese patient with laron syndrome

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

Bases Genéticas dos Distúrbios de Crescimento

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