Molekulargenetisches Labor
Zentrum für Nephrologie und Stoffwechsel
Moldiag Erkrankungen Gene Support Kontakt

Störungen der Regulation des Wachstums

In dieser Gruppe werden Erkrankungen zusammengefasst die auf einer Gestörten Wachstumshormonwirkung beruhen. Dabei können Störungen auf den verschiedensten Ebenen der Wachstumshormon-Signalkaskade liegen. Vom Releasing Hormon über das Wachstumshormon bis hin zum Somatomedin C (IGF1) genannten Zytokin. In jedem dieser Signalschritte kann wiederum sowohl das Hormon als auch der Rezeptor betroffen sein.

Pathogenese

Error occured.
Wachstumshormon Signalkaskade

Labortest

Für alle Laborteste gilt das Störungen innerhalb der Wachstumshormon-Signalkaskade meist zu einer Erhöhung der Hormonwerte stromauf und einer Erniedrigung strommab führen.

Parameter Interpretation
GHRH Erniedrigt bei Störungen in Hypothalamus
GH Erniedrigt bei Störungen in der Hypophyse
IGF1 Erniedrigt bei Störungen in GH-Signalverarbeitung in peripheren Zellen
TSH,LH,ACTH,FSH Erniedrigt bei Störungen der gesamten Hypophyse

Gliederung

Erbliche endokrinologische Erkrankungen
Autoimmune Polyendokrinopathie
Erbliche Erkrankungen der Hypophyse
Erkrankungen der Nebenschilddrüse
Genetische Erkrankungen der Hypophyse
Genetische Erkrankungen der Nebenniere
Hereditärer Diabetes insipidus
Multiple endokrine Neoplasie 1
Nierenerkrankungen mit endokrinologischer Manifestation
Störungen der Regulation des Wachstums
ADAMTSL3
Kombinierter Hypophysenhormon-Mangel
Hyophysenhormonmangel Typ 1
POU1F1
Hyophysenhormonmangel Typ 2
PROP1
Hyophysenhormonmangel Typ 3
LHX3
Hyophysenhormonmangel Typ 4
LHX4
Hyophysenhormonmangel Typ 5
HESX1
Wachstumshormon-Mangel
GH1
Isolierter dominanter Wachstumshormonmangel
GH1
Isolierter rezessiver Wachstumshormonmangel Typ 1A
GH1
Isolierter rezessiver Wachstumshormonmangel Typ 1B
GH1
GHRH
GHRHR
Isolierter x-chromosomaler Wachstumshormonmangel
BTK
Kowarski-Syndrom
GH1
Wachstumshormon-Sekretagogum-Resistenz
GHSR
Wachstumshormon-Unempfindlichkeit
IGFBP3
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
GHR
Störungen der Sexualentwicklung
Störungen des Schilddrüsenhormonsystems

Referenzen:

1.

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

external link
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.

external link
3.

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

external link
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.

external link
5.

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

external link
6.

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

external link
7.

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).

external link
8.

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

external link
9.

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

external link
10.

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.

external link
11.

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

external link
12.

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.

external link
13.

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

external link
14.

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

external link
15.

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

external link
16.

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.

external link
17.

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

external link
18.

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

external link
19.

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

external link
20.

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

external link
21.

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.

external link
22.

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

external link
23.

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

external link
24.

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

external link
25.

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

external link
26.

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.

external link
27.

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

external link
28.

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.

external link
29.

None (2003) Insulin-like growth factors and the basis of growth.

external link
30.

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

external link
31.

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

external link
32.

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.

external link
33.

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

external link
34.

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

external link
35.

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

external link
36.

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

external link
37.

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

external link
38.

None (2007) Insulin-like growth factor-1 potentiates platelet activation via the IRS/PI3Kalpha pathway.

external link
39.

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

external link
40.

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

external link
41.

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.

external link
42.

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

external link
43.

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

external link
44.

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

external link
45.

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

external link
46.

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

external link
47.

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

external link
48.

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

external link
49.

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

external link
50.

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.

external link
51.

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

external link
52.

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.

external link
53.

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

external link
54.

None (1986) Two insulin-like growth factor I messenger RNAs are expressed in human liver.

external link
55.

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

external link
56.

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.

external link
57.

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

external link
58.

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

external link
59.

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

external link
60.

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

external link
61.

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

external link
62.

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

external link
63.

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

external link
64.

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

external link
65.

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

external link
66.

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.

external link
67.

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

external link
68.

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

external link
69.

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

external link
70.

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

external link
71.

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

external link
72.

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.

external link
73.

None (1998) Insulin-like growth factor-I and new opportunities for cancer prevention.

external link
74.

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

external link
75.

de Groof F et al. (2002) Acute stress response in children with meningococcal sepsis: important differences in the growth hormone/insulin-like growth factor I axis between nonsurvivors and survivors.

external link
76.

Goossens M et al. (1986) Isolated growth hormone (GH) deficiency type 1A associated with a double deletion in the human GH gene cluster.

external link
77.

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

external link
78.

Millar DS et al. (2003) Novel mutations of the growth hormone 1 (GH1) gene disclosed by modulation of the clinical selection criteria for individuals with short stature.

external link
79.

Takahashi Y et al. (1996) Brief report: short stature caused by a mutant growth hormone.

external link
80.

Mendlewicz J et al. (1999) Genetic control of 24-hour growth hormone secretion in man: a twin study.

external link
81.

Hayashi Y et al. (1999) Inhibition of growth hormone (GH) secretion by a mutant GH-I gene product in neuroendocrine cells containing secretory granules: an implication for isolated GH deficiency inherited in an autosomal dominant manner.

external link
82.

Hindmarsh PC et al. (1999) A sexually dimorphic pattern of growth hormone secretion in the elderly.

external link
83.

Saitoh H et al. (1999) A Japanese family with autosomal dominant growth hormone deficiency.

external link
84.

Kamijo T et al. (1999) Mutations in intron 3 of GH-1 gene associated with isolated GH deficiency type II in three Japanese families.

external link
85.

Leiberman E et al. (2000) Short stature in carriers of recessive mutation causing familial isolated growth hormone deficiency.

external link
86.

Abdul-Latif H et al. (2000) Growth hormone deficiency type IB caused by cryptic splicing of the GH-1 gene.

external link
87.

Hasegawa Y et al. (2000) Identification of novel human GH-1 gene polymorphisms that are associated with growth hormone secretion and height.

external link
88.

Moseley CT et al. (2002) An exon splice enhancer mutation causes autosomal dominant GH deficiency.

external link
89.

Ho Y et al. (2002) A defined locus control region determinant links chromatin domain acetylation with long-range gene activation.

external link
90.

Takahashi I et al. (2002) An exonic mutation of the GH-1 gene causing familial isolated growth hormone deficiency type II.

external link
91.

Fofanova OV et al. (2003) A novel IVS2 -2A>T splicing mutation in the GH-1 gene in familial isolated growth hormone deficiency type II in the spectrum of other splicing mutations in the Russian population.

external link
92.

Horan M et al. (2003) Human growth hormone 1 (GH1) gene expression: complex haplotype-dependent influence of polymorphic variation in the proximal promoter and locus control region.

external link
93.

Ryther RC et al. (2003) Disruption of exon definition produces a dominant-negative growth hormone isoform that causes somatotroph death and IGHD II.

external link
94.

Wolfrum C et al. (2003) Role of Foxa-2 in adipocyte metabolism and differentiation.

external link
95.

Akinci A et al. (1992) Isolated growth hormone (GH) deficiency type IA associated with a 45-kilobase gene deletion within the human GH gene cluster.

external link
96.

Lewis MD et al. (2004) A novel dysfunctional growth hormone variant (Ile179Met) exhibits a decreased ability to activate the extracellular signal-regulated kinase pathway.

external link
97.

Dennison EM et al. (2004) Polymorphism in the growth hormone gene, weight in infancy, and adult bone mass.

external link
98.

Mullis PE et al. (2005) Isolated autosomal dominant growth hormone deficiency: an evolving pituitary deficit? A multicenter follow-up study.

external link
99.

Besson A et al. (2005) Short stature caused by a biologically inactive mutant growth hormone (GH-C53S).

external link
100.

Mullis PE et al. (1992) Prevalence of human growth hormone-1 gene deletions among patients with isolated growth hormone deficiency from different populations.

external link
101.

Vivenza D et al. (2006) A novel deletion in the GH1 gene including the IVS3 branch site responsible for autosomal dominant isolated growth hormone deficiency.

external link
102.

Ho Y et al. (2006) Locus control region transcription plays an active role in long-range gene activation.

external link
103.

Petkovic V et al. (2007) Evaluation of the biological activity of a growth hormone (GH) mutant (R77C) and its impact on GH responsiveness and stature.

external link
104.

Ge G et al. (2007) Bone morphogenetic protein 1 processes prolactin to a 17-kDa antiangiogenic factor.

external link
105.

Petkovic V et al. (2007) Exon splice enhancer mutation (GH-E32A) causes autosomal dominant growth hormone deficiency.

external link
106.

Hess O et al. (2007) Variable phenotypes in familial isolated growth hormone deficiency caused by a G6664A mutation in the GH-1 gene.

external link
107.

Giordano M et al. (2008) A functional common polymorphism in the vitamin D-responsive element of the GH1 promoter contributes to isolated growth hormone deficiency.

external link
108.

Shariat N et al. (2008) Isolated growth hormone deficiency type II caused by a point mutation that alters both splice site strength and splicing enhancer function.

external link
109.

He YA et al. (1990) A Chinese familial growth hormone deficiency with a deletion of 7.1 kb of DNA.

external link
110.

Vnencak-Jones CL et al. (1990) Use of polymerase chain reaction in detection of growth hormone gene deletions.

external link
111.

Chen EY et al. (1989) The human growth hormone locus: nucleotide sequence, biology, and evolution.

external link
112.

Masuda N et al. (1988) Molecular cloning of cDNA encoding 20 kDa variant human growth hormone and the alternative splicing mechanism.

external link
113.

Vnencak-Jones CL et al. (1988) Molecular basis of human growth hormone gene deletions.

external link
114.

Fiddes JC et al. (1979) Structure of genes for human growth hormone and chorionic somatomammotropin.

external link
115.

Braga S et al. (1986) Familial growth hormone deficiency resulting from a 7.6 kb deletion within the growth hormone gene cluster.

external link
116.

Xu WM et al. (1988) Construction of a genetic map of human chromosome 17 by use of chromosome-mediated gene transfer.

external link
117.

Morgan JR et al. (1987) Expression of an exogenous growth hormone gene by transplantable human epidermal cells.

external link
118.

Martial JA et al. (1979) Human growth hormone: complementary DNA cloning and expression in bacteria.

external link
119.

Cooke NE et al. (1986) The related genes encoding growth hormone and prolactin have been dispersed to chromosomes 10 and 17 in the rat.

external link
120.

Niall HD et al. (1971) Sequences of pituitary and placental lactogenic and growth hormones: evolution from a primordial peptide by gene reduplication.

external link
121.

Chakravarti A et al. (1984) Patterns of polymorphism and linkage disequilibrium suggest independent origins of the human growth hormone gene cluster.

external link
122.

George DL et al. (1981) The genes for growth hormone and chorionic somatomammotropin are on the long arm of human chromosome 17 in region q21 to qter.

external link
123.

Harper ME et al. (1982) Chromosomal localization of the human placental lactogen-growth hormone gene cluster to 17q22-24.

external link
124.

Owerbach D et al. (1980) Genes for growth hormone, chorionic somatommammotropin, and growth hormones-like gene on chromosome 17 in humans.

external link
125.

Sirand-Pugnet P et al. (1995) An intronic (A/U)GGG repeat enhances the splicing of an alternative intron of the chicken beta-tropomyosin pre-mRNA.

external link
126.

Binder G et al. (1995) Screening for growth hormone (GH) gene splice-site mutations in sporadic cases with severe isolated GH deficiency using ectopic transcript analysis.

external link
127.

Phillips JA et al. (1994) Genetic basis of endocrine disease. 6. Molecular basis of familial human growth hormone deficiency.

external link
128.

Igarashi Y et al. (1993) A new mutation causing inherited growth hormone deficiency: a compound heterozygote of a 6.7 kb deletion and a two base deletion in the third exon of the GH-1 gene.

external link
129.

Cogan JD et al. (1993) Heterogeneous growth hormone (GH) gene mutations in familial GH deficiency.

external link
130.

Jones BK et al. (1995) The human growth hormone gene is regulated by a multicomponent locus control region.

external link
131.

Cogan JD et al. (1995) A recurring dominant negative mutation causes autosomal dominant growth hormone deficiency--a clinical research center study.

external link
132.

Binder G et al. (1996) Mechanisms responsible for dominant expression of human growth hormone gene mutations.

external link
133.

Sundström M et al. (1996) Crystal structure of an antagonist mutant of human growth hormone, G120R, in complex with its receptor at 2.9 A resolution.

external link
134.

Cogan JD et al. (1997) A novel mechanism of aberrant pre-mRNA splicing in humans.

external link
135.

Smith LE et al. (1997) Essential role of growth hormone in ischemia-induced retinal neovascularization.

external link
136.

Takahashi Y et al. (1997) Biologically inactive growth hormone caused by an amino acid substitution.

external link
137.

Boguszewski CL et al. (1997) Increased proportion of circulating non-22-kilodalton growth hormone isoforms in short children: a possible mechanism for growth failure.

external link
138.

Behncken SN et al. (1997) Aspartate 171 is the major primate-specific determinant of human growth hormone. Engineering porcine growth hormone to activate the human receptor.

external link
139.

Gertner JM et al. (1998) Genetic defects in the control of growth hormone secretion.

external link
140.

McCarthy EM et al. (1998) Characterization of an intron splice enhancer that regulates alternative splicing of human GH pre-mRNA.

external link
Update: 14. August 2020
Copyright © 2005-2020 Zentrum für Nephrologie und Stoffwechsel, Dr. Mato Nagel
Albert-Schweitzer-Ring 32, D-02943 Weißwasser, Deutschland, Tel.: +49-3576-287922, Fax: +49-3576-287944
Seitenüberblick | Webmail | Haftungsausschluss | Datenschutz