Best Practice & Research Clinical Endocrinology & Metabolism
Volume 20, Issue 4 , Pages 501-513 , December 2006

Mutations in the Gs alpha gene causing hormone resistance

  • Giovanna Mantovani, MD (Postdoctoral fellow)

      Affiliations

    • Corresponding Author InformationCorresponding author. Tel.: +39 02 50320613; Fax: +39 02 50320605.

References 

  1. Spiegel AM, Shenker A, Weinstein LS. Receptor-effector coupling by G proteins: implications for normal and abnormal signal transduction. Endocrine Reviews. 1992;13:536–565
  2. Dhanasekaran N, Heasley LE, Johnson GL. G protein-coupled receptor systems involved in cell growth and oncogenesis. Endocrine Reviews. 1995;16:259–270
  3. Spiegel AM. Mutations in G proteins and G protein-coupled receptors in endocrine disease. The Journal of Clinical Endocrinology and Metabolism. 1996;81:2434–2442
  4. Farzel A, Bourne HR, Tahor I. The expanding spectrum of G protein diseases. The New England Journal of Medicine. 1999;340:1012–1019
  5. Lania A, Mantovani G, Spada A. G protein mutations in endocrine diseases. European Journal of Endocrinology. 2001;145:543–559
  6. Spada A, Vallar L, Faglia G. G protein oncogene in pituitary tumors. Trends in Endocrinology and Metabolism. 1992;3:355–360
  7. Wettschureck N, Offermanns S. Mammalian G proteins and their cell type specific functions. Physiological Reviews. 2005;85:1159–1204
  8. Dryja TP, Hahn LB, Reboul T, et al. Missense mutation in the gene encoding the alpha subunit of rod transducin in the Nougaret form of congenital stationary night blindness. Nature Genetics. 1996;13:358–360
  9. Weinstein LS, Liu J, Sakamoto A, et al. Minireview: GNAS: normal and abnormal functions. Endocrinolology. 2004;145:5459–5464
  10. Albright F, Burnett CH, Smith CH, et al. Pseudohypoparathyroidism: an example of ‘Sebright-Bantam sindrome’. Endocrinology. 1942;30:922–932
  11. Tashjian AH, Frantz AG, Lee JB. Pseudohypoparathyroidism: assays of parathyroid hormone and thyrocalcitonin. Proceedings of the National Academy of Sciences of the USA. 1966;56:1138–1142
  12. Mann JB, Alterman S, Hills AG. Albright's hereditary osteodystrophy comprising pseudohypoparathyroidism and pseudopseudohypoparathyroidism with a report of two cases representing the complete syndrome occurring in successive generations. Annals of Internal Medicine. 1962;56:315–342
  13. Eyre WG, Reed WB. Albright hereditary osteodystrophy with cutaneous bone formation. Archives of Dermatology. 1971;104:634–642
  14. Farfel Z, Friedman E. Mental deficiency in pseudohypoparathyroidism type I is associated with Ns-protein deficiency. Annals of Internal Medicine. 1986;105:197–199
  15. Albright F, Forbes AP, Henneman PH. Pseudopseudohypoparathyroidism. Transactions of the Association of American Physicians. 1952;65:337–350
  16. Farfel Z, Brothers VM, Brickman AS, et al. Pseudohypoparathyroidism: inheritance of deficient receptor-cyclase coupling activity. Proceedings of National Academy of Sciences USA. 1981;78:3098–3102
  17. Fitch N. Albright's hereditary osteodistrophy: a Review. American Journal of Medical Genetics. 1982;11:11–29
  18. Weinberg AG, Stone RT. Autosomal dominant inheritance in Albright's hereditary osteodystrophy. The Journal of Pediatrics. 1971;79:996–999
  19. Chase LR, Melson GL, Aurbach GD. Pseudohypoparathyroidism: defective excretion of 3′, 5′-AMP in response to parathyroid hormone. The Journal of Clinical Investigation. 1969;48:1832–1844
  20. Aurbach GD, Marx SJ, Spiegel AM. Parathyroid Hormone, Calcitonin, and the calciferols. In:  Wilson JD,  Foster DW editor. Williams textbook of Endocrinology. 8th ed. Philadelphia: Saunders; 1992;p. 1397–1476
  21. Levine MA, Downs RW, Singer M, et al. Deficient activity of guanine nucleotide regulatory protein in erythrocytes from patients with pseudohypoparathyroidism. Biochemical and Biophysical Research Communications. 1980;94:1319–1324
  22. Farfel Z, Brickman AS, Kaslow HR, et al. Defect of receptor-cyclase coupling protein in pseudohypoparathyroidism. The New England Journal of Medicine. 1980;303:237–242
  23. Levine MA, Downs RW, Moses AM, et al. Resistance to multiple hormones in patients with pseudohypoparathyroidism: association with deficient activity of guanine nucleotide regulatory protein. The American Journal of Medicine. 1983;74:545–556
  24. Radeke HH, Auf'mkolk B, Juppner H, et al. Multiple pre- and postreceptor defects in pseudohypoparathyroidism (a multicenter study with 24 patients). The Journal of Clinical Endocrinology and Metabolism. 1986;62:393–402
  25. Barrett D, Breslau NA, Wax MB, et al. New form of pseudohypoparathyroidism with abnormal catalytic adenylate cyclase. The American Journal of Physiology. 1989;257:E277–E283
  26. Silve C, Santora A, Breslau NA, et al. Selective resistance to parathyroid hormone in cultured skin fibroblasts from patients with pseudohypoparathyroidism type Ib. The Journal of Clinical Endocrinology and Metabolism. 1986;62:640–644
  27. Wemeau JL, Balavoine AS, Ladsous M, et al. Multihormonal resistance to parathyroid hormone, thyroid stimulatin hormone, and other hormonal and neurosensory stimuli in patients with pseudohypoparathyroidism. Journal of Pediatric Endocrinology and Metabolism. 2006;19:253–261
  28. Germain-Lee EL. Short stature, obesity, and growth hormone deficiency in pseudohypoparathyroidism type Ia. Pediatric Endocrinology Reviews. 2006;3:318–326
  29. Weinstein LS, Yu S, Warner DR, et al. Endocrine manifestations of stimulatory G protein alpha-subunit mutations and the role of genomic imprinting. Endocrine Reviews. 2001;22:675–705
  30. Mantovani G, Spada A. Resistance to growth hormone releasing hormone and gonadotropins in Albright's hereditary osteodystrophy. Journal of Pediatric Endocrinology and Metabolism. 2006;19:663–670
  31. Mantovani G, Maghnie M, Weber G, et al. Growth hormone-releasing hormone resistance in pseudohypoparathyroidism type Ia: new evidence for imprinting of the Gs alpha gene. The Journal of Clinical Endocrinology and Metabolism. 2003;88:4070–4074
  32. Germain-Lee EL, Groman J, Crane JL, et al. Growth hormone deficiency in pseudohypoparathyroidism type 1a: another manifestation of multihormone resistance. The Journal of Clinical Endocrinology and Metabolism. 2003;88:4059–4069
  33. Levine MA, Jap TS, Mauseth RS, et al. Activity of the stimulatory guanine nucleotide-binding protein is reduced in erythrocytes from patients with pseudohypoparathyroidism and pseudopseudohypoparathyroidism: biochemical, endocrine, and genetic analysis of Albright's hereditary osteodystrophy in six kindreds. The Journal of Clinical Endocrinology and Metabolism. 1986;62:497–502
  34. Fischer JA, Bourne HR, Dambacher MA, et al. Pseudohypoparathyroidism: inheritance and expression of deficient receptor-cyclase coupling protein activity. Clinical Endocrinology. 1983;19:747–754
  35. Wilson LC, Leverton K, Luttikhuis ME, et al. Brachydactyly and mental retardation: an Albright's hereditary osteodystrophy-like syndrome localized to 2q37. American Journal of Human Genetics. 1995;56:400–407
  36. Phelan MC, Rogers RC, Clarkson KB, et al. Albright's hereditary osteodystrophy and del(2) (q37.3) in four unrelated individuals. American Journal of Human Genetics. 1995;58:1–7
  37. Weinstein LS. Albright hereditary osteodystrophy, pseudohypoparathyroidism, and Gs deficiency. In:  Spiegel AM editors. G proteins, receptors, and disease. Totowa, New Jersey: Humana Press; 1998;p. 23–56
  38. Moses AM, Weinstock RS, Levine MA, Breslau NA. Evidence for normal antidiuretic responses to endogenous and exogenous arginine vasopressein in patients with guanine nucleotide-binding stimulatory protein-deficient pseudohypoparathyroidism. The Journal of Clinical Endocrinology and Metabolism. 1986;62:221–224
  39. Faull CM, Welbury RR, Paul B, et al. Pseudohypoparathyroidism: its phenotypic variability and associated disorders in a large family. The Quarterly Journal of Medicine. 1991;78:251–264
  40. Pattern JL, Johns DR, Valle D, et al. Mutation in the gene encoding the stimulatory G protein of adenylate cyclase in Albright's hereditary osteodystrophy. The New England Journal of Medicine. 1990;322:1412–1419
  41. OMIM entry 139320. http://www.ncbi.nlm.nih.gov
  42. Gejman PV, Weinstein LS, Martinez M, et al. Genetic mapping of the Gs α-subunit gene (GNAS1) to the distal long arm of chromosome 20 using a polymorphism detected by denaturating gradient gel electrophoresis. Genomics. 1991;9:782–783
  43. Weinstein LS, Gejman PB, Mazancourt P, et al. A heterozygous 4-bp deletion mutation in the Gs alpha gene (GNAS1) in a patient with Albright's hereditary osteodystrophy. Genomics. 1992;13:1319–1321
  44. Ahmed SF, Dixon PH, Bonthron DT, et al. GNAS1 mutational analysis in pseudohypoparathyroidism. Clinical Endocrinology. 1998;49:525–531
  45. Mantovani G, Romoli R, Weber G, et al. Mutational analysis of GNAS1 in patients with pseudohypoparathyroidism: identification of two novel mutations. The Journal of Clinical Endocrinology and Metabolism. 2000;85:4243–4248
  46. Aldred MA, Trembath RC. Activating and inactivating mutations in the human GNAS1 gene. Human Mutation. 2000;16:183–189
  47. Yokoyama M, Takeda K, Iyota K, et al. A 4-bp deletion mutation of Gs alpha gene in a Japanese patient with pseudoparathyroidism. Journal of Endocrinological Investigation. 1996;19:236–241
  48. Yu SH, Yu D, Hainline BE, et al. A deletion hot-spot in exon 7 of the Gsα gene (GNAS1) in patients with Albright hereditary osteodystrophy. Human Molecular Genetics. 1995;4:2001–2002
  49. Krawczak M, Cooper DN. Gene deletions causing human genetic disease: mechanisms of mutagenesis and the role of the local DNA sequence environment. Human Genetics. 1991;86:425–441
  50. Nakamoto JM, Jones EA, Zimmerman D, et al. A missense mutation in the Gsα gene is associated with pseudohypoparathyroidism Ia (PHP-Ia) and gonadotropin-independent precocious puberty (GIPP). Clinical Research. 1993;41:40A
  51. Iiri T, Herzmark P, Nakamoto JM, et al. Rapid GDP release from Gs alpha in patients with gain and loss of endocrine function. Nature. 1994;371:164–168
  52. Winter JS, Hughes IA. Familial pseudohypoparathyroidism without somatic anomalies. Canadian Medical Association Journal. 1986;123:26–31
  53. Nusynowitz ML, Frame B, Kolb FO. The spectrum of the hypoparathyroid states: a classification based on physiologic principles. Medicine. 1976;55:105–119
  54. Liu J, Erlichman B, Weinstein LS. The stimulatory G protein alpha-subunit Gs alpha is imprinted in human thyroid glands: implications for thyroid function in pseudohypoparathyroidism types 1A and 1B. The Journal of Clinical Endocrinology and Metabolism. 2003;88:4336–4341
  55. Schipani E, Weinstein LS, Bergwitz C, et al. Pseudohypoparathyroidism type Ib is not caused by mutations in the coding exons of the human parathyroid hormone (PTH)/PTH-related peptide receptor gene. The Journal of Clinical Endocrinology and Metabolism. 1995;80:1611–1621
  56. Bettoun JD, Minagawa M, Kwan MY, et al. Cloning and characterization of the promoter regions of the human parathyroid hormone (PTH)/PTH-related peptide receptor gene: analysis of deoxyribonucleic acid from normal subjects and patients with pseudohypoparathyroidism. The Journal of Clinical Endocrinology and Metabolism. 1997;82:1031–1040
  57. Fukumoto S, Suzawa M, Takeuchi Y, et al. Absence of mutations in parathyroid hormone (PTH)/PTH-related protein receptor complementary deoxyribonucleic acid in patients with pseudohypoparathyroidism type Ib. The Journal of Clinical Endocrinology and Metabolism. 1996;81:2554–2558
  58. Lanske B, Karaplis AC, Lee K, et al. PTH/PTHrP receptor in early development and Indian hedgehog-regulated bone growth. Science. 1996;273:663–666
  59. Jobert AS, Zhang P, Couvineau A, et al. Absence of functional receptors for parathyroid hormone and parathyroid hormone-related peptide in Blomstrand chondrodisplasia. The Journal of Clinical Investigation. 1998;102:34–40
  60. Juppner H, Schipani E, Bastepe M, et al. The gene responsible for pseudohypoparathyroidism type Ib is paternally imprinted and maps in four unrelated kindreds to chromosome 20q13.3. Proceedings of the National Academy of Sciences of the USA. 1998;95:11798–11803
  61. Wu WI, Schwindinger WF, Aparicio LF, Levine MA. Selective resistance to parathyroid hormone caused by a novel uncoupling mutation in the carboxyl terminus of Gsα: a cause of pseudohypoparathyroidism type Ib. The Journal of Biological Chemistry. 2001;276:165–171
  62. Liu J, Litman D, Rosenberg MJ, et al. A GNAS1 imprinting defect in pseudohypoparathyroidism type Ib. The Journal of Clinical Investigation. 2000;106:1167–1174
  63. Bastepe M, Pincus JE, Sugimoto T, et al. Positional dissociation between the genetic mutation responsible for pseudohypoparathyroidism type Ib and the associated methylation defect at exon A/B: Evidence for a long-range regulatory element within the imprinted GNAS1 locus. Human Molecular Genetics. 2001;10:1231–1241
  64. Bastepe M, Frohlich LF, Hendy GN, et al. Autosomal dominant pseudohypoparathyroidism type Ib is associated with a heterozygous microdeletion that likely disrupts a putative imprinting control element of GNAS. The Journal of Clinical Investigation. 2003;112:1255–1263
  65. Linglart A, Gensure RC, Olney RC, et al. A novel STX16 deletion in autosomal dominant pseudohypoparathyroidism type Ib redefines the boundaries of a cis-acting imprinting control element of GNAS. American Journal of Human Genetics. 2005;76:804–814
  66. Bastepe M, Frohlich LF, Linglart A, et al. Deletion of the NESP55 differentially methylated region causes loss of maternal GNAS imprints and pseudohypoparathyroidism type Ib. Nature Genetics. 2005;37:25–27
  67. Liu J, Nealon JG, Weinstein LS. Distinct patterns of abnormal GNAS imprinting in familial and sporadic pseudohypoparathyroidism type IB. Human Molecular Genetics. 2005;14:95–102
  68. Drezner M, Neelon FA, Lebovitz HE. Pseudohypoparathyroidism type II: a possible defect in the reception of the cyclic AMP signal. The New England Journal of Medicine. 1973;289:1056–1060
  69. Rao DS, Parfitt AM, Kleerecoper M, et al. Dissociation between the effects of endogenous parathyroid hormone on adenosine 3′, 5′-monophosphate generation and phosphate reabsorption in hypocalcemia due to vitamin D depletion: an acquired disorder resembling pseudohypoparathyoidism type II. The Journal of Clinical Endocrinology and Metabolism. 1985;61:285–290
  70. Rodriguez HJ, Villareal H, Klahr S, et al. Pseudohypoparathyroidism type II: restoration of normal renal responsiveness to parathyroid hormone by calcium administration. The Journal of Clinical Endocrinology and Metabolism. 1974;39:693–701
  71. Bartolomei MS, Tilgham SM. Genomic imprinting in mammals. Annual Review of Genetics. 1997;31:493–525
  72. Cattanach BM, Kirk M. Differential activity of maternally and paternally derived chromosome regions in mice. Nature. 1985;315:496–498
  73. Yu S, Yu D, Lee E, et al. Variable and tissue-specific hormone resistance in heterotrimeric Gs protein α-subunit (Gsα) knockout mice is due to tissue-specific imprinting of the Gsα gene. Proceedings of the National Academy of Sciences of the USA. 1998;95:8715–8720
  74. Weinstein LS, Yu S, Ecelbarger CA. Variable imprinting of the heterotrimeric G protein Gsα-subunit within different segments of the nephron. The American Journal of Physiology. 2000;278:F507–F514
  75. Hayward BE, Bonthron DT. An imprinted antisense transcript at the human GNAS1 locus. Human Molecular Genetics. 2000;9:835–841
  76. Hayward BE, Kamiya M, Strain L, et al. The human GNAS1 gene is imprinted and encodes distinct paternally and biallelically expressed G proteins. Proceedings of the National Academy of Sciences of the USA. 1998;95:10038–10043
  77. Hayward BE, Moran V, Strain L, et al. Bidirectional imprinting of a single gene: GNAS1 encodes maternally, paternally and biallelically derived proteins. Proceedings of the National Academy of Sciences of the USA. 1998;95:15475–15480
  78. Peters J, Wroe SF, Wells CA, et al. A cluster of oppositely imprinted transcripts at the Gnas locus in the distal imprinting region of mouse chromosome 2. Proceedings of the National Academy of Sciences of the USA. 1999;96:3830–3835
  79. Liu J, Yu S, Litman D, et al. Identification of a methylation imprint mark within the mouse Gnas locus. Molecular and Cellular Biology. 2000;20:5808–5817
  80. Mantovani G, Ballare E, Giammona E, et al. The Gsα gene: predominant maternal origin of transcription in human thyroid gland and gonads. The Journal of Clinical Endocrinology and Metabolism. 2002;87:4736–4740
  81. Germain-Lee EL, Ding CL, Deng Z, et al. Paternal imprinting of Galpha(s) in the human thyroid as the basis of TSH resistance in pseudohypoparathyroidism type 1a. Biochemical and Biophysical Research Communications. 2002;296:67–72
  82. Liu J, Erlichman B, Weinstein LS. The stimulatory G protein α-subunit Gsα is imprinted in human thyroid glands: Implications for thyroid function in pseudohypoparathyroidism types 1A and 1B. The Journal of Clinical Endocrinology and Metabolismol. 2003;88:4336–4341
  83. Hayward BE, Barlier A, Korbonits M, et al. Imprinting of the Gαs gene GNAS1 in the pathogenesis of acromegaly. The Journal of Clinical Investigation. 2001;107:R31–R36

PII: S1521-690X(06)00072-8

doi: 10.1016/j.beem.2006.09.001

Best Practice & Research Clinical Endocrinology & Metabolism
Volume 20, Issue 4 , Pages 501-513 , December 2006

Article Tools

* Image Usage & Resolution