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Wachstumshormonrezeptor

Das GHR-Gen kodiert den Wachtumshormonrezeptor, ein transmembranöser Rezeptor der Zytokinrezeptorfamilie 1. Durch die Bindung an Wachstumshormon kommt es zu einer Dimerisierung und einer Signaltraduktion in die Zelle. Dabei werden weitere Wachstumsstimulierende Faktoren (Somatomedine) freigesetzt. Am bekanntensten is Somatomedin C auch als IGF1 bekannt. Die Inaktivierung des Rezeptors erfolgt unter anderem durch die Abspaltung des extrazellulären hormonbindenen Anteils. Dieser Anteil ist als Wachstumshormonbindendes Protein (GHBP) im Serum nachweisbar. Mutationen können zu einem verminderten Ansprechen, wie beim autosomal rezessiven Laron-Syndrom oder bei der autosomal dominanten Wachstumshormonresistenz, einem vermehrten Ansprechen, wie bei der Wachstumshormonhypersensitivität, und zu Hypercholesterinämien führen.

Genstruktur

Ein häufiger Polymorphismus in diesem gen ist die Deletion des gesamten Exons 3. Diese Variante wird als GHRd3 bezeichnet und dem vorhandenen Exon 3 mit der Bezeichnung GHRfl gegenübergestellt. Die Häufigkeit der drei möglichen Genotypen beträgt GHRfl/GHRfl 35-53%, GHRfl/GHRd3 33–58% und GHRd3/ GHRd3 7-26%. Ein stärkeres ansprechen auf Wachstumshormon wurde bei der Variante GHRd3 beobachtet. Dieser Polymorphismus ist in der Evolution wahrscheinlich durch eine Retrovirusinfektion entstanden.[Error: Macro 'ref' doesn't exist]

Gentests:

Klinisch Untersuchungsmethoden Familienuntersuchung
Bearbeitungszeit 5 Tage
Probentyp genomische DNS
Klinisch Untersuchungsmethoden Hochdurchsatz-Sequenzierung
Bearbeitungszeit 25 Tage
Probentyp genomische DNS
Klinisch Untersuchungsmethoden Direkte Sequenzierung der proteinkodierenden Bereiche eines Gens
Bearbeitungszeit 25 Tage
Probentyp genomische DNS
Klinisch Untersuchungsmethoden Multiplex ligationsabhängige Amplifikation
Bearbeitungszeit 20 Tage
Probentyp genomische DNS

Verknüpfte Erkrankungen:

Laron-Syndrom
GHR
Wachstumshormon-Überempfindlichkeit
GHR

Referenzen:

1.

Spencer SA et al. (1988) Rabbit liver growth hormone receptor and serum binding protein. Purification, characterization, and sequence.

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2.

Schreiner F et al. (2007) Association of the growth hormone receptor d3-variant and catch-up growth of preterm infants with birth weight of less than 1500 grams.

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3.

Carrascosa A et al. (2008) Growth hormone (GH) dose, but not exon 3-deleted/full-length GH receptor polymorphism genotypes, influences growth response to two-year GH Therapy in Short Small-for-Gestational-Age Children.

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4.

Räz B et al. (2008) Influence of growth hormone (GH) receptor deletion of exon 3 and full-length isoforms on GH response and final height in patients with severe GH deficiency.

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5.

van der Klaauw AA et al. (2008) Influence of the d3-growth hormone (GH) receptor isoform on short-term and long-term treatment response to GH replacement in GH-deficient adults.

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6.

Audí L et al. (2008) The exon 3-deleted/full-length growth hormone receptor polymorphism does not influence the effect of puberty or growth hormone therapy on glucose homeostasis in short non-growth hormone-deficient small-for-gestational-age children: results from a two-year controlled prospective study.

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7.

Mercado M et al. (2008) Clinical and biochemical impact of the d3 growth hormone receptor genotype in acromegaly.

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8.

Amselem S et al. (1991) Recurrent nonsense mutations in the growth hormone receptor from patients with Laron dwarfism.

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9.

Rubin CJ et al. (2010) Whole-genome resequencing reveals loci under selection during chicken domestication.

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10.

Rosenbloom AL et al. (1990) The little women of Loja--growth hormone-receptor deficiency in an inbred population of southern Ecuador.

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11.

Arden KC et al. (1990) The receptors for prolactin and growth hormone are localized in the same region of human chromosome 5.

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12.

Barton DE et al. (1989) Chromosome mapping of the growth hormone receptor gene in man and mouse.

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13.

Amselem S et al. (1989) Laron dwarfism and mutations of the growth hormone-receptor gene.

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14.

Laron Z et al. (1989) Serum GH binding protein activities identifies the heterozygous carriers for Laron type dwarfism.

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15.

Godowski PJ et al. (1989) Characterization of the human growth hormone receptor gene and demonstration of a partial gene deletion in two patients with Laron-type dwarfism.

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16.

Leung DW et al. () Growth hormone receptor and serum binding protein: purification, cloning and expression.

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17.

Goddard AD et al. (1995) Mutations of the growth hormone receptor in children with idiopathic short stature. The Growth Hormone Insensitivity Study Group.

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18.

Edery M et al. (1993) Lack of hormone binding in COS-7 cells expressing a mutated growth hormone receptor found in Laron dwarfism.

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19.

Berg MA et al. (1993) Diverse growth hormone receptor gene mutations in Laron syndrome.

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20.

Woods KA et al. (1996) A homozygous splice site mutation affecting the intracellular domain of the growth hormone (GH) receptor resulting in Laron syndrome with elevated GH-binding protein.

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21.

Stallings-Mann ML et al. (1996) Alternative splicing of exon 3 of the human growth hormone receptor is the result of an unusual genetic polymorphism.

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22.

Menon RK et al. (1997) Identification and characterization of single strand DNA-binding protein that represses growth hormone receptor gene expression.

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23.

Kaji H et al. (1997) Novel compound heterozygous mutations of growth hormone (GH) receptor gene in a patient with GH insensitivity syndrome.

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24.

Amit T et al. (1997) A membrane-fixed, truncated isoform of the human growth hormone receptor.

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25.

Iida K et al. (1998) Growth hormone (GH) insensitivity syndrome with high serum GH-binding protein levels caused by a heterozygous splice site mutation of the GH receptor gene producing a lack of intracellular domain.

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26.

Kranzler JH et al. (1998) Normal intelligence with severe insulin-like growth factor I deficiency due to growth hormone receptor deficiency: a controlled study in a genetically homogeneous population.

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27.

Rosenbloom AL et al. (1998) Stature in Ecuadorians heterozygous for growth hormone receptor gene E180 splice mutation does not differ from that of homozygous normal relatives.

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28.

Shen XY et al. (1998) Cirrhotic liver expresses low levels of the full-length and truncated growth hormone receptors.

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29.

Walker JL et al. (1998) A novel mutation affecting the interdomain link region of the growth hormone receptor in a Vietnamese girl, and response to long-term treatment with recombinant human insulin-like growth factor-I and luteinizing hormone-releasing hormone analogue.

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30.

Sanchez JE et al. (1998) Growth hormone receptor mutations in children with idiopathic short stature.

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31.

Wojcik J et al. (1998) Four contiguous amino acid substitutions, identified in patients with Laron syndrome, differently affect the binding affinity and intracellular trafficking of the growth hormone receptor.

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32.

Sobrier ML et al. (1993) Expression and binding properties of two isoforms of the human growth hormone receptor.

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33.

Jensen RB et al. (2007) The presence of the d3-growth hormone receptor polymorphism is negatively associated with fetal growth but positively associated with postnatal growth in healthy subjects.

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34.

Horan M et al. (2006) Genetic variation at the growth hormone (GH1) and growth hormone receptor (GHR) loci as a risk factor for hypertension and stroke.

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35.

Takada D et al. (2003) Growth hormone receptor variant (L526I) modifies plasma HDL cholesterol phenotype in familial hypercholesterolemia: intra-familial association study in an eight-generation hyperlipidemic kindred.

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36.

Ayling RM et al. (1997) A dominant-negative mutation of the growth hormone receptor causes familial short stature.

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37.

Iida K et al. (1999) Functional characterization of truncated growth hormone (GH) receptor-(1-277) causing partial GH insensitivity syndrome with high GH-binding protein.

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38.

Shuto Y et al. (1999) Reduced growth hormone receptor messenger ribonucleic acid in an aged man with chronic malnutrition and growth hormone resistance.

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39.

Amit T et al. (2000) Clinical review 112: Does serum growth hormone (GH) binding protein reflect human GH receptor function?

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40.

Pantel J et al. (2000) Species-specific alternative splice mimicry at the growth hormone receptor locus revealed by the lineage of retroelements during primate evolution.

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41.

Ballesteros M et al. (2000) Distribution and abundance of messenger ribonucleic acid for growth hormone receptor isoforms in human tissues.

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42.

Stofega MR et al. (2000) Mutation of the SHP-2 binding site in growth hormone (GH) receptor prolongs GH-promoted tyrosyl phosphorylation of GH receptor, JAK2, and STAT5B.

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43.

Gastier JM et al. (2000) Diverse deletions in the growth hormone receptor gene cause growth hormone insensitivity syndrome.

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44.

Leung KC et al. (2000) Insulin regulation of human hepatic growth hormone receptors: divergent effects on biosynthesis and surface translocation.

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45.

Fisker S et al. (2001) Gene expression of a truncated and the full-length growth hormone (GH) receptor in subcutaneous fat and skeletal muscle in GH-deficient adults: impact of GH treatment.

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46.

Metherell LA et al. (2001) Pseudoexon activation as a novel mechanism for disease resulting in atypical growth-hormone insensitivity.

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47.

Jorge AA et al. (2002) Poor reproducibility of IGF-I and IGF binding protein-3 generation test in children with short stature and normal coding region of the GH receptor gene.

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48.

Marzullo P et al. (2002) Leptin concentrations in GH deficiency: the effect of GH insensitivity.

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49.

Berg MA et al. (1992) Mutation creating a new splice site in the growth hormone receptor genes of 37 Ecuadorean patients with Laron syndrome.

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50.

Asa SL et al. (2007) A growth hormone receptor mutation impairs growth hormone autofeedback signaling in pituitary tumors.

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51.

Fang P et al. (2007) Primary growth hormone (GH) insensitivity and insulin-like growth factor deficiency caused by novel compound heterozygous mutations of the GH receptor gene: genetic and functional studies of simple and compound heterozygous states.

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52.

Duquesnoy P et al. (1991) Defective membrane expression of human growth hormone (GH) receptor causes Laron-type GH insensitivity syndrome.

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53.

David A et al. (2007) An intronic growth hormone receptor mutation causing activation of a pseudoexon is associated with a broad spectrum of growth hormone insensitivity phenotypes.

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54.

Kenth G et al. (2007) Relationship of the human growth hormone receptor exon 3 genotype with final adult height and bone mineral density.

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55.

Audí L et al. (2006) Exon 3-deleted/full-length growth hormone receptor polymorphism genotype frequencies in Spanish short small-for-gestational-age (SGA) children and adolescents (n = 247) and in an adult control population (n = 289) show increased fl/fl in short SGA.

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56.

Carrascosa A et al. (2006) The d3/fl-growth hormone (GH) receptor polymorphism does not influence the effect of GH treatment (66 microg/kg per day) or the spontaneous growth in short non-GH-deficient small-for-gestational-age children: results from a two-year controlled prospective study in 170 Spanish patients.

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57.

Binder G et al. (2006) The d3-growth hormone (GH) receptor polymorphism is associated with increased responsiveness to GH in Turner syndrome and short small-for-gestational-age children.

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58.

Jorge AA et al. (2006) Growth hormone (GH) pharmacogenetics: influence of GH receptor exon 3 retention or deletion on first-year growth response and final height in patients with severe GH deficiency.

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59.

Greenhalgh CJ et al. (2005) SOCS2 negatively regulates growth hormone action in vitro and in vivo.

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60.

Tiulpakov A et al. (2005) A novel C-terminal growth hormone receptor (GHR) mutation results in impaired GHR-STAT5 but normal STAT-3 signaling.

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61.

Dos Santos C et al. (2004) A common polymorphism of the growth hormone receptor is associated with increased responsiveness to growth hormone.

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62.

Milward A et al. (2004) Growth hormone (GH) insensitivity syndrome due to a GH receptor truncated after Box1, resulting in isolated failure of STAT 5 signal transduction.

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63.

Fielder PJ et al. (1992) Expression of serum insulin-like growth factors, insulin-like growth factor-binding proteins, and the growth hormone-binding protein in heterozygote relatives of Ecuadorian growth hormone receptor deficient patients.

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64.

Pantel J et al. (2003) Heterozygous nonsense mutation in exon 3 of the growth hormone receptor (GHR) in severe GH insensitivity (Laron syndrome) and the issue of the origin and function of the GHRd3 isoform.

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65.

OMIM.ORG article

Omim 600946 external link
66.

Orphanet article

Orphanet ID 122095 external link
67.

NCBI article

NCBI 2690 external link
68.

Wikipedia Artikel

Wikipedia DE (Somatotropin-Rezeptor) external link
Update: 14. August 2020
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