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==== GH1 gene mutations ====
==== GH1 gene mutations ====
* It is ''GH1'' is the gene encoding GH, located on [[chromosome 17]].
* ''GH1'' gene encoding GH is located on [[chromosome 17]].
* [[Gene deletion|Gene deletions]], f[[Frameshift mutation|rameshift]] mutations, and [[nonsense mutations]] of ''GH1'' have been described as causes of familial GHD.
* [[Gene deletion|Gene deletions]], f[[Frameshift mutation|rameshift]] mutations, and [[nonsense mutations]] of ''GH1'' have been described as causes of familial GHD.



Revision as of 19:13, 11 October 2017

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohammed Abdelwahed M.D[2]

Overview

The somatotroph cells of the anterior pituitary gland produce growth hormone (GH). GH best-known effect is increasing body mass. GH causes epiphyseal plate widening and cartilage growth. GH deficiency results in alterations in the physiology of different systems of the body, manifesting as altered lipid metabolism, increased subcutaneous visceral fat, decreased muscle mass. Genetic basis of congenital growth hormone deficiency depends on many genes, for example, POU1F1 gene mutations are the most common known genetic cause of the combined pituitary hormone deficiency. Gene deletions, frameshift mutations, and nonsense mutations of GH1 gene have been described as causes of familial GHD.

Pathophysiology

  • GH deficiency results in alterations in the physiology of different systems of the body, manifesting as altered lipid metabolism, increased subcutaneous visceral fat, decreased muscle mass, decreased bone density, low exercise performance, and reduced quality of life.

Regulation of growth hormone secretion

Growth hormone secretion regulations, source: By OpenStax College - Anatomy & Physiology, Connexions Web site. httpcnx.orgcontentcol114961.6, Jun 19, 2013., CC BY 3.0, httpscommons.wikimedia.orgwindex.phpcurid=30148146

Molecular effects of growth hormone on cells

Growth hormone peripheral action, source: By Mikael Häggström.When using this image in external works, it may be cited asHäggström, Mikael (2014). Medical gallery of Mikael Häggström 2014. WikiJournal of Medicine 1 (2). DOI10.15347wjm2014.008. ISSN 2002-4436
GH signaling

Genetic basis of growth hormone deficiency

POU1F1 gene mutations

GH1 gene mutations

Syndrome of bioinactive GH

GH receptor signal transduction

  • It is essential for normal signaling of the GH receptor. Mutations in the gene encoding signal transducer decrease the response of receptors to GH.[8]

IGF-I gene mutations

Defective stabilization of circulating IGF-I

  • Acid-labile subunit is important for the stabilization of the IGF-I.
  • Mutations in the gene coding for it causes less stable and subsequently less effect.[10]

IGF-I receptor mutations

References

  1. Cuttler L (1996). "The regulation of growth hormone secretion". Endocrinol Metab Clin North Am. 25 (3): 541–71. PMID 8879986.
  2. MURPHY WR, DAUGHADAY WH, HARTNETT C (1956). "The effect of hypophysectomy and growth hormone on the incorporation of labeled sulfate into tibial epiphyseal and nasal cartilage of the rat". J Lab Clin Med. 47 (5): 715–22. PMID 13319878.
  3. Veldhuis JD, Roemmich JN, Richmond EJ, Rogol AD, Lovejoy JC, Sheffield-Moore M; et al. (2005). "Endocrine control of body composition in infancy, childhood, and puberty". Endocr Rev. 26 (1): 114–46. doi:10.1210/er.2003-0038. PMID 15689575.
  4. Ziemnicka K, Budny B, Drobnik K, Baszko-Błaszyk D, Stajgis M, Katulska K; et al. (2016). "Two coexisting heterozygous frameshift mutations in PROP1 are responsible for a different phenotype of combined pituitary hormone deficiency". J Appl Genet. 57 (3): 373–81. doi:10.1007/s13353-015-0328-z. PMC 4963446. PMID 26608600.
  5. Li S, Crenshaw EB, Rawson EJ, Simmons DM, Swanson LW, Rosenfeld MG (1990). "Dwarf locus mutants lacking three pituitary cell types result from mutations in the POU-domain gene pit-1". Nature. 347 (6293): 528–33. doi:10.1038/347528a0. PMID 1977085.
  6. Wu W, Cogan JD, Pfäffle RW, Dasen JS, Frisch H, O'Connell SM; et al. (1998). "Mutations in PROP1 cause familial combined pituitary hormone deficiency". Nat Genet. 18 (2): 147–9. doi:10.1038/ng0298-147. PMID 9462743.
  7. Besson A, Salemi S, Deladoëy J, Vuissoz JM, Eblé A, Bidlingmaier M; et al. (2005). "Short stature caused by a biologically inactive mutant growth hormone (GH-C53S)". J Clin Endocrinol Metab. 90 (5): 2493–9. doi:10.1210/jc.2004-1838. PMID 15713716.
  8. Hwa V, Camacho-Hübner C, Little BM, David A, Metherell LA, El-Khatib N; et al. (2007). "Growth hormone insensitivity and severe short stature in siblings: a novel mutation at the exon 13-intron 13 junction of the STAT5b gene". Horm Res. 68 (5): 218–24. doi:10.1159/000101334. PMID 17389811.
  9. Batey L, Moon JE, Yu Y, Wu B, Hirschhorn JN, Shen Y; et al. (2014). "A novel deletion of IGF1 in a patient with idiopathic short stature provides insight Into IGF1 haploinsufficiency". J Clin Endocrinol Metab. 99 (1): E153–9. doi:10.1210/jc.2013-3106. PMC 3879666. PMID 24243634.
  10. Domené HM, Hwa V, Argente J, Wit JM, Wit JM, Camacho-Hübner C; et al. (2009). "Human acid-labile subunit deficiency: clinical, endocrine and metabolic consequences". Horm Res. 72 (3): 129–41. doi:10.1159/000232486. PMID 19729943.
  11. Kawashima Y, Higaki K, Fukushima T, Hakuno F, Nagaishi J, Hanaki K; et al. (2012). "Novel missense mutation in the IGF-I receptor L2 domain results in intrauterine and postnatal growth retardation". Clin Endocrinol (Oxf). 77 (2): 246–54. doi:10.1111/j.1365-2265.2012.04357.x. PMID 22309212.