Molekulargenetische Diagnostik
Praxis Dr. Mato Nagel

Wachstumshormon-Unempfindlichkeit

Die Wachstumshormon-Unempfindlichkeit fasst Störungen zusammen, bei denen die Wirkungslosigkeit des Hormons einen Wachstumsschub auszulosen das gemeinsame Merkmal ist.

Geschichtliches

Die Resistenz gegenüber Wachstumshormon wurde 1966 von Laron erstmalig beschrieben. Er beschrieb eine konsanguine jüdische Familie aus dem Jemen mit 3 etrem wachtstumsretardierten Kindern. Bei den Betroffenen fanden sich eher erhöhte Wachstumshormonspiegel.[1]

Im Jahr 1989 urde mit der Entdeckung und vollständigen beschreibung des Gens die Möglichkeit eröffnet, die Erkrankung molekulargenetisch zu beschreiben.[2]

Die Dual effector Hypothese brachte den Durchbruch beim Verständnis der Wachstumhormonkontrolle. Sie wurde vim Jahr 1985 von Green entwickelt. Nach dieser Hypothese stimuliert Wachtsumshormon die lokale IGF1-produktion, welche dann in einer autocrinen oder paracrinen Weise die lokalen Wachstumsprozesse anschiebt.[3]

Gliederung

Störungen der Regulation des Wachstums
Kleinwuchs, SHOX-bedingt
Kombinierter Hypophysenhormon-Mangel
Syndromale Wachstumsstörung
Wachstumshormon-Mangel
Wachstumshormon-Unempfindlichkeit
Insulinähnlicher Wachtumsfaktor 1 Mangel
IGF1
Insulinähnlicher Wachtumsfaktor 1 Resistenz
IGF1R
Insulinähnlicher Wachtumsfaktor 1-Transportproteinmangel
IGFALS
Laron-Syndrom
GHR
SH2B1
Wachstumshormoninsensitivität mit Immundefizit
STAT5B
Wachstumshormon-Überempfindlichkeit

Referenzen:

1.

Lin SC et al. (1993) Molecular basis of the little mouse phenotype and implications for cell type-specific growth.

[^]
2.

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.

[^]
3.

Maor SB et al. (2000) BRCA1 suppresses insulin-like growth factor-I receptor promoter activity: potential interaction between BRCA1 and Sp1.

[^]
4.

Rasmussen SK et al. (2000) Studies of the variability of the genes encoding the insulin-like growth factor I receptor and its ligand in relation to type 2 diabetes mellitus.

[^]
5.

Tatar M et al. (2001) A mutant Drosophila insulin receptor homolog that extends life-span and impairs neuroendocrine function.

[^]
6.

Rotem-Yehudar R et al. (2001) Association of insulin-like growth factor 1 receptor with EHD1 and SNAP29.

[^]
7.

Fernández AM et al. (2001) Functional inactivation of the IGF-I and insulin receptors in skeletal muscle causes type 2 diabetes.

[^]
8.

All-Ericsson C et al. (2002) Insulin-like growth factor-1 receptor in uveal melanoma: a predictor for metastatic disease and a potential therapeutic target.

[^]
9.

Kulkarni RN et al. (2002) beta-cell-specific deletion of the Igf1 receptor leads to hyperinsulinemia and glucose intolerance but does not alter beta-cell mass.

[^]
10.

Scott BA et al. (2002) Regulation of hypoxic death in C. elegans by the insulin/IGF receptor homolog DAF-2.

[^]
11.

Holzenberger M et al. (2003) IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice.

[^]
12.

Lambooij AC et. al. (2003) Insulin-like growth factor-I and its receptor in neovascular age-related macular degeneration.

[^]
13.

Giovannone B et al. (2003) Two novel proteins that are linked to insulin-like growth factor (IGF-I) receptors by the Grb10 adapter and modulate IGF-I signaling.

[^]
14.

Kondo T et al. (2003) Knockout of insulin and IGF-1 receptors on vascular endothelial cells protects against retinal neovascularization.

[^]
15.

Bonafè M et al. (2003) Polymorphic variants of insulin-like growth factor I (IGF-I) receptor and phosphoinositide 3-kinase genes affect IGF-I plasma levels and human longevity: cues for an evolutionarily conserved mechanism of life span control.

[^]
16.

Abbott AM et al. (1992) Insulin-like growth factor I receptor gene structure.

[^]
17.

Prager D et al. (1992) Human insulin-like growth factor I receptor function in pituitary cells is suppressed by a dominant negative mutant.

[^]
18.

Nef S et al. (2003) Testis determination requires insulin receptor family function in mice.

[^]
19.

Abuzzahab MJ et al. (2003) IGF-I receptor mutations resulting in intrauterine and postnatal growth retardation.

[^]
20.

Okubo Y et al. (2003) Cell proliferation activities on skin fibroblasts from a short child with absence of one copy of the type 1 insulin-like growth factor receptor (IGF1R) gene and a tall child with three copies of the IGF1R gene.

[^]
21.

Wessells RJ et al. (2004) Insulin regulation of heart function in aging fruit flies.

[^]
22.

Kawashima Y et al. (2005) Mutation at cleavage site of insulin-like growth factor receptor in a short-stature child born with intrauterine growth retardation.

[^]
23.

Raile K et al. (2006) Clinical and functional characteristics of the human Arg59Ter insulin-like growth factor i receptor (IGF1R) mutation: implications for a gene dosage effect of the human IGF1R.

[^]
24.

Ueki K et al. (2006) Total insulin and IGF-I resistance in pancreatic beta cells causes overt diabetes.

[^]
25.

Poduslo SE et al. (1991) Detecting high-resolution polymorphisms in human coding loci by combining PCR and single-strand conformation polymorphism (SSCP) analysis.

[^]
26.

Lou M et al. (2006) The first three domains of the insulin receptor differ structurally from the insulin-like growth factor 1 receptor in the regions governing ligand specificity.

[^]
27.

Salehi-Ashtiani K et al. (2006) A genomewide search for ribozymes reveals an HDV-like sequence in the human CPEB3 gene.

[^]
28.

Cooke DW et al. (1991) Analysis of the human type I insulin-like growth factor receptor promoter region.

[^]
29.

Inagaki K et al. (2007) A familial insulin-like growth factor-I receptor mutant leads to short stature: clinical and biochemical characterization.

[^]
30.

Bendall SC et al. (2007) IGF and FGF cooperatively establish the regulatory stem cell niche of pluripotent human cells in vitro.

[^]
31.

Suh Y et al. (2008) Functionally significant insulin-like growth factor I receptor mutations in centenarians.

[^]
32.

Walenkamp MJ et al. (2008) Successful long-term growth hormone therapy in a girl with haploinsufficiency of the insulin-like growth factor-I receptor due to a terminal 15q26.2->qter deletion detected by multiplex ligation probe amplification.

[^]
33.

Roback EW et al. (1991) An infant with deletion of the distal long arm of chromosome 15 (q26.1----qter) and loss of insulin-like growth factor 1 receptor gene.

[^]
34.

Herskowitz I et al. () Functional inactivation of genes by dominant negative mutations.

[^]
35.

Ullrich A et al. (1986) Insulin-like growth factor I receptor primary structure: comparison with insulin receptor suggests structural determinants that define functional specificity.

[^]
36.

Flier JS et al. (1986) Monoclonal antibody to the type I insulin-like growth factor (IGF-I) receptor blocks IGF-I receptor-mediated DNA synthesis: clarification of the mitogenic mechanisms of IGF-I and insulin in human skin fibroblasts.

[^]
37.

Francke U et al. (1986) Chromosomal mapping of genes involved in growth control.

[^]
38.

Howard TK et al. (1993) The insulin-like growth factor 1 receptor gene is normally biallelically expressed in human juvenile tissue and tumours.

[^]
39.

Ogawa O et al. (1993) Human insulin-like growth factor type I and type II receptors are not imprinted.

[^]
40.

Liu JP et al. (1993) Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r).

[^]
41.

Werner H et al. (1996) Wild-type and mutant p53 differentially regulate transcription of the insulin-like growth factor I receptor gene.

[^]
42.

Dey BR et al. (1998) Cloning of human p55 gamma, a regulatory subunit of phosphatidylinositol 3-kinase, by a yeast two-hybrid library screen with the insulin-like growth factor-I receptor.

[^]
43.

Grant ES et al. (1998) The insulin-like growth factor type I receptor stimulates growth and suppresses apoptosis in prostatic stromal cells.

[^]
44.

Aleman A et al. (1999) Insulin-like growth factor-I and cognitive function in healthy older men.

[^]
45.

Sjögren K et al. (1999) Liver-derived insulin-like growth factor I (IGF-I) is the principal source of IGF-I in blood but is not required for postnatal body growth in mice.

[^]
46.

Yakar S et al. (1999) Normal growth and development in the absence of hepatic insulin-like growth factor I.

[^]
47.

Vestergaard P et al. (1999) Effect of sex hormone replacement on the insulin-like growth factor system and bone mineral: a cross-sectional and longitudinal study in 595 perimenopausal women participating in the Danish Osteoporosis Prevention Study.

[^]
48.

Semsarian C et al. (1999) Skeletal muscle hypertrophy is mediated by a Ca2+-dependent calcineurin signalling pathway.

[^]
49.

Musarò A et al. (1999) IGF-1 induces skeletal myocyte hypertrophy through calcineurin in association with GATA-2 and NF-ATc1.

[^]
50.

Playford MP et al. (2000) Insulin-like growth factor 1 regulates the location, stability, and transcriptional activity of beta-catenin.

[^]
51.

Harman SM et al. (2000) Serum levels of insulin-like growth factor I (IGF-I), IGF-II, IGF-binding protein-3, and prostate-specific antigen as predictors of clinical prostate cancer.

[^]
52.

Yanovski JA et al. (2000) Insulin-like growth factors and bone mineral density in African American and White girls.

[^]
53.

Le Roith D et al. (2001) What is the role of circulating IGF-I?

[^]
54.

Musarò A et al. (2001) Localized Igf-1 transgene expression sustains hypertrophy and regeneration in senescent skeletal muscle.

[^]
55.

Hellstrom A et al. (2001) Low IGF-I suppresses VEGF-survival signaling in retinal endothelial cells: direct correlation with clinical retinopathy of prematurity.

[^]
56.

Smith PJ et al. (2002) An exonic splicing enhancer in human IGF-I pre-mRNA mediates recognition of alternative exon 5 by the serine-arginine protein splicing factor-2/alternative splicing factor.

[^]
57.

Barton ER et al. (2002) Muscle-specific expression of insulin-like growth factor I counters muscle decline in mdx mice.

[^]
58.

Vaessen N et al. (2002) Association between genetic variation in the gene for insulin-like growth factor-I and low birthweight.

[^]
59.

Arends N et al. (2002) Polymorphism in the IGF-I gene: clinical relevance for short children born small for gestational age (SGA).

[^]
60.

Humbert S et al. (2002) The IGF-1/Akt pathway is neuroprotective in Huntington's disease and involves Huntingtin phosphorylation by Akt.

[^]
61.

Simó R et al. (2002) Free insulin growth factor-I and vascular endothelial growth factor in the vitreous fluid of patients with proliferative diabetic retinopathy.

[^]
62.

Carro E et al. (2002) Serum insulin-like growth factor I regulates brain amyloid-beta levels.

[^]
63.

Geary MP et al. (2003) Sexual dimorphism in the growth hormone and insulin-like growth factor axis at birth.

[^]
64.

Johnston LB et al. (2003) Association between insulin-like growth factor I (IGF-I) polymorphisms, circulating IGF-I, and pre- and postnatal growth in two European small for gestational age populations.

[^]
65.

Rosenfeld RG et al. (2003) Insulin-like growth factors and the basis of growth.

[^]
66.

Bonapace G et al. (2003) A novel mutation in a patient with insulin-like growth factor 1 (IGF1) deficiency.

[^]
67.

Sussenbach JS et al. (1992) Structure and expression of the human insulin-like growth factor genes.

[^]
68.

Usala AL et al. (1992) Brief report: treatment of insulin-resistant diabetic ketoacidosis with insulin-like growth factor I in an adolescent with insulin-dependent diabetes.

[^]
69.

Ruberte J et al. (2004) Increased ocular levels of IGF-1 in transgenic mice lead to diabetes-like eye disease.

[^]
70.

Walenkamp MJ et al. (2005) Homozygous and heterozygous expression of a novel insulin-like growth factor-I mutation.

[^]
71.

Kurosu H et. al. (2005) Suppression of aging in mice by the hormone Klotho.

[^]
72.

Sutter NB et al. (2007) A single IGF1 allele is a major determinant of small size in dogs.

[^]
73.

Kim S et al. (2007) Insulin-like growth factor-1 regulates platelet activation through PI3-Kalpha isoform.

[^]
74.

Hers I et al. (2007) Insulin-like growth factor-1 potentiates platelet activation via the IRS/PI3Kalpha pathway.

[^]
75.

Johansson M et al. (2007) Implications for prostate cancer of insulin-like growth factor-I (IGF-I) genetic variation and circulating IGF-I levels.

[^]
76.

Kim SW et al. (1991) Structure and function of a human insulin-like growth factor-I gene promoter.

[^]
77.

Mullis PE et al. (1991) Growth characteristics and response to growth hormone therapy in patients with hypochondroplasia: genetic linkage of the insulin-like growth factor I gene at chromosome 12q23 to the disease in a subgroup of these patients.

[^]
78.

Schoenle EJ et al. (1991) Recombinant human insulin-like growth factor I (rhIGF I) reduces hyperglycaemia in patients with extreme insulin resistance.

[^]
79.

Justice MJ et al. (1990) A genetic linkage map of mouse chromosome 10: localization of eighteen molecular markers using a single interspecific backcross.

[^]
80.

Taylor BA et al. (1991) Localization of the gene encoding insulin-like growth factor I on mouse chromosome 10.

[^]
81.

Pouladi MA et al. (2010) Full-length huntingtin levels modulate body weight by influencing insulin-like growth factor 1 expression.

[^]
82.

Mayack SR et al. (2010) Systemic signals regulate ageing and rejuvenation of blood stem cell niches.

[^]
83.

Takano K et al. (2010) Nebulin and N-WASP cooperate to cause IGF-1-induced sarcomeric actin filament formation.

[^]
84.

Bowcock A et al. (1990) Polymorphism and mapping of the IGF1 gene, and absence of association with stature among African Pygmies.

[^]
85.

Rapp R et al. (1988) Characterization of the protein which binds insulin-like growth factor in human serum.

[^]
86.

Guler HP et al. (1989) Small stature and insulin-like growth factors: prolonged treatment of mini-poodles with recombinant human insulin-like growth factor I.

[^]
87.

Le Bouc Y et al. (1986) Complete characterization of the human IGF-I nucleotide sequence isolated from a newly constructed adult liver cDNA library.

[^]
88.

Rotwein P et al. (1986) Organization and sequence of the human insulin-like growth factor I gene. Alternative RNA processing produces two insulin-like growth factor I precursor peptides.

[^]
89.

Höppener JW et al. (1985) The human gene encoding insulin-like growth factor I is located on chromosome 12.

[^]
90.

Rotwein P et al. (1986) Two insulin-like growth factor I messenger RNAs are expressed in human liver.

[^]
91.

Mathews LS et al. (1986) Regulation of insulin-like growth factor I gene expression by growth hormone.

[^]
92.

Morton CC et al. (1986) Human genes for insulin-like growth factors I and II and epidermal growth factor are located on 12q22----q24.1, 11p15, and 4q25----q27, respectively.

[^]
93.

Daughaday WH et al. (1972) Somatomedin: proposed designation for sulphation factor.

[^]
94.

Ullrich A et al. (1984) Isolation of the human insulin-like growth factor I gene using a single synthetic DNA probe.

[^]
95.

Rinderknecht E et al. (1978) The amino acid sequence of human insulin-like growth factor I and its structural homology with proinsulin.

[^]
96.

Jansen M et al. () Sequence of cDNA encoding human insulin-like growth factor I precursor.

[^]
97.

Brissenden JE et al. () Human chromosomal mapping of genes for insulin-like growth factors I and II and epidermal growth factor.

[^]
98.

Tricoli JV et al. () Localization of insulin-like growth factor genes to human chromosomes 11 and 12.

[^]
99.

Li CH et al. (1983) Total synthesis of insulin-like growth factor I (somatomedin C).

[^]
100.

Svoboda ME et al. (1980) Purification of somatomedin-C from human plasma: chemical and biological properties, partial sequence analysis, and relationship to other somatomedins.

[^]
101.

Copeland KC et al. (1980) Induction of immunoreactive somatomedin C human serum by growth hormone: dose-response relationships and effect on chromatographic profiles.

[^]
102.

Van Wyk JJ et al. (1980) Evidence from radioligand assays that somatomedin-C and insulin-like growth factor-I are similar to each other and different from other somatomedins.

[^]
103.

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

[^]
104.

Powell-Braxton L et al. (1993) IGF-I is required for normal embryonic growth in mice.

[^]
105.

Baker J et al. (1993) Role of insulin-like growth factors in embryonic and postnatal growth.

[^]
106.

Woods KA et al. (1996) Intrauterine growth retardation and postnatal growth failure associated with deletion of the insulin-like growth factor I gene.

[^]
107.

Lembo G et al. (1996) Elevated blood pressure and enhanced myocardial contractility in mice with severe IGF-1 deficiency.

[^]
108.

Zhu J et al. (1997) Analysis of a peptide hormone-receptor interaction in the yeast two-hybrid system.

[^]
109.

Bianda T et al. (1998) Effects of short-term insulin-like growth factor-I (IGF-I) or growth hormone (GH) treatment on bone metabolism and on production of 1,25-dihydroxycholecalciferol in GH-deficient adults.

[^]
110.

Holly J et al. (1998) Insulin-like growth factor-I and new opportunities for cancer prevention.

[^]
111.

Hankinson SE et al. (1998) Circulating concentrations of insulin-like growth factor-I and risk of breast cancer.

[^]
112.

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.

[^]
113.

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

[^]
114.

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

[^]
115.

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.

[^]
116.

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

[^]
117.

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.

[^]
118.

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

[^]
119.

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

[^]
120.

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.

[^]
121.

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

[^]
122.

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.

[^]
123.

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

[^]
124.

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.

[^]
125.

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

[^]
126.

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.

[^]
127.

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.

[^]
128.

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.

[^]
129.

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

[^]
130.

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

[^]
131.

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

[^]
132.

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.

[^]
133.

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.

[^]
134.

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.

[^]
135.

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.

[^]
136.

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

[^]
137.

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.

[^]
138.

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

[^]
139.

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.

[^]
140.

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.

[^]
141.

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

[^]
142.

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.

[^]
143.

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.

[^]
144.

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.

[^]
145.

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.

[^]
146.

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.

[^]
147.

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

[^]
148.

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

[^]
149.

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

[^]
150.

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

[^]
151.

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

[^]
152.

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

[^]
153.

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

[^]
154.

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

[^]
155.

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.

[^]
156.

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

[^]
157.

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

[^]
158.

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

[^]
159.

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

[^]
160.

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.

[^]
161.

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.

[^]
162.

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

[^]
163.

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

[^]
164.

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

[^]
165.

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

[^]
166.

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.

[^]
167.

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.

[^]
168.

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.

[^]
169.

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

[^]
170.

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.

[^]
171.

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

[^]
172.

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.

[^]
173.

Green H et al. (1985) A dual effector theory of growth-hormone action.

[^]
174.

Laron Z et al. () Genetic pituitary dwarfism with high serum concentation of growth hormone--a new inborn error of metabolism?

[^]