GNAS-related loss-of-function disorders and the role of imprinting

Hormone Research in Paediatrics

Volumn 79, Issue 3, 2013, Pages 119-129

  Linglart, Agnès ^a,b   Maupetit Méhouas, Stéphanie ^c   Silve, Caroline ^a,b  

^a Fr Ctr of Ref for Rare Disord of Calcium and Phosphorus Metab   (France)

^b INSERM   (France)

^c UNIVERSITÉ CLERMONT AUVERGNE   (France)

Author keywords

GNAS; Imprinting; Parathyroid hormone; Pseudohypoparathyroidism

Indexed keywords

BISPHOSPHONIC ACID DERIVATIVE; CALCITRIOL; CALCIUM; CANNABINOID 1 RECEPTOR ANTAGONIST; CYCLIC AMP; CYCLIC AMP DEPENDENT PROTEIN KINASE; G PROTEIN COUPLED RECEPTOR; GUANINE NUCLEOTIDE BINDING PROTEIN; NONSTEROID ANTIINFLAMMATORY AGENT; PARATHYROID HORMONE; PHOSPHATE; THIOSULFATE; THYROTROPIN; GNAS PROTEIN, HUMAN; STIMULATORY GUANINE NUCLEOTIDE BINDING PROTEIN; STX16 PROTEIN, HUMAN; SYNTAXIN 16;

ALBRIGHT SYNDROME; CALCIUM BLOOD LEVEL; DISEASE TRANSMISSION; DNA METHYLATION; FOLLOW UP; GENE EXPRESSION; GENE MUTATION; GENE SEQUENCE; GENETIC COUNSELING; GENOME IMPRINTING; GROWTH ACCELERATION; HAPLOINSUFFICIENCY; HAPLOTYPE; HETEROTOPIC OSSIFICATION; HETEROZYGOTE; HORMONE RESISTANCE; HUMAN; HYPERCALCIURIA; LIFESTYLE; LOSS OF FUNCTION MUTATION; MENTAL DEFICIENCY; MOLECULAR BIOLOGY; MOLECULAR DIAGNOSIS; OBESITY; OSTEODYSTROPHY; PHENOTYPE; PHOSPHATE BLOOD LEVEL; PRENATAL DIAGNOSIS; PRIMARY HYPERPARATHYROIDISM; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN FUNCTION; REVIEW; UNIPARENTAL DISOMY; VITAMIN D DEFICIENCY; ALLELE; GENETIC DISORDER; GENETICS; METABOLISM; MUTATION; OPEN READING FRAME;

ALLELES; GENETIC DISEASES, INBORN; GENOMIC IMPRINTING; GTP-BINDING PROTEIN ALPHA SUBUNITS, GS; HUMANS; MUTATION; OPEN READING FRAMES; SYNTAXIN 16;

EID: 84875650111     PISSN: 16632818     EISSN: 16632826     Source Type: Journal    
DOI: 10.1159/000348516     Document Type: Review

References (65)

1. Albright F, Burnett CH, Smith PH, Parson W: Pseudohypoparathyroidism-an example of 'seabright-bantam syndrome'. Endocrinology 1942; 30: 922-932.
2. Werder EA, Fischer JA, Illig R, Kind HP, Bernasconi S, Fanconi A, Prader A: Pseudohypoparathyroidism and idiopathic hypoparathyroidism: relationship between serum calcium and parathyroid hormone levels and urinary cyclic adenosine-3,5′ -monophosphate response to parathyroid extract. J Clin Endocrinol Metab 1978; 46: 872-879.
3. Weinstein LS, Gejman PV, Friedman E, Kadowaki T, Collins RM, Gershon ES, Spiegel AM: Mutations of the Gsα-subunit gene in Albright hereditary osteodystrophy detected by denaturing gradient gel electrophoresis. Proc Natl Acad Sci USA 1990; 87: 8287-8290.
4. Liu J, Litman D, Rosenberg M, Yu S, Biesecker L, Weinstein L: A GNAS1 imprinting defect in pseudohypoparathyroidism type Ib. J Clin Invest 2000; 106: 1167-1174.
5. Levine MA: Pseudohypoparathyroidism; in Bilezikian JP, Raisz LG, Rodan GA (eds): Principles of Bone Biology. New York, Academic Press, 2002, vol 2, pp 1137-1163.
6. Linglart A, Menguy C, Couvineau A, Auzan C, Gunes Y, Cancel M, Motte E, Pinto G, Chanson P, Bougneres P, Clauser E, Silve C: Recurrent PRKAR1A mutation in acrodysostosis with hormone resistance. N Engl J Med 2011; 364: 2218-2226.
7. Michot C, Le Goff C, Goldenberg A, Abhyankar A, Klein C, Kinning E, Guerrot AM, Flahaut P, Duncombe A, Baujat G, Lyonnet S, Thalassinos C, Nitschke P, Casanova JL, Le Merrer M, Munnich A, Cormier-Daire V: Exome sequencing identifies PDE4D mutations as another cause of acrodysostosis. Am J Hum Genet 2012; 90: 740-745.
8. Lee H, Graham JM Jr, Rimoin DL, Lachman RS, Krejci P, Tompson SW, Nelson SF, Krakow D, Cohn DH: Exome sequencing identifies PDE4D mutations in acrodysostosis. Am J Hum Genet 2012; 90: 746-751.
9. Ideraabdullah F, Vigneau S, Bartolomei MS: Genomic imprinting mechanisms in mammals. Mutat Res 2008; 647: 77-85.
10. Bastepe M: The GNAS locus and pseudohypoparathyroidism. Adv Exp Med Biol 2008; 626: 27-40.
11. Hayward BE, Moran V, Strain L, Bonthron DT: Bidirectional imprinting of a single gene: GNAS1 encodes maternally, paternally, and biallelically derived proteins. Proc Natl Acad Sci USA 1998; 95: 15475-15480.
12. 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. J Clin Endocrinol Metab 2003; 88: 4336-4341.
13. Mantovani G, Ballare E, Giammona E, Beck- Peccoz P, Spada A: The Gsα gene: predominant maternal origin of transcription in human thyroid gland and gonads. J Clin Endocrinol Metab 2002; 87: 4736-4740.
14. Hayward B, Barlier A, Korbonits M, Grossman A, Jacquet P, Enjalbert A, Bonthron D: Imprinting of the G(s)α gene GNAS1 in the pathogenesis of acromegaly. J Clin Invest 2001; 107:R31-R36.
15. Bastepe M, Frohlich LF, Hendy GN, Indridason OS, Josse RG, Koshiyama H, Korkko J, Nakamoto JM, Rosenbloom AL, Slyper AH, Sugimoto T, Tsatsoulis A, Crawford JD, Juppner H: Autosomal dominant pseudohypoparathyroidism type Ib is associated with a heterozygous microdeletion that likely disrupts a putative imprinting control element of GNAS. J Clin Invest 2003; 112: 1255-1263.
16. Bastepe M, Frohlich LF, Linglart A, Abu-Zahra HS, Tojo K, Ward LM, Juppner H: Deletion of the NESP55 differentially methylated region causes loss of maternal GNAS imprints and pseudohypoparathyroidism type Ib. Nat Genet 2005; 37: 25-27.
17. Richard N, Abeguile G, Coudray N, Mittre H, Gruchy N, Andrieux J, Cathebras P, Kottler ML: A new deletion ablating NESP55 causes loss of maternal imprint of A/B GNAS and autosomal dominant pseudohypoparathyroidism type Ib. J Clin Endocrinol Metab 2012; 97:E863-E867.
18. Chillambhi S, Turan S, Hwang D, Chen H, Juppner H, Bastepe M: Deletion of the GNAS antisense transcript result in parent-of-origin specific GNAS imprinting defects and phenotypes including PTH resistance. American Association for Bone and Mineral Metabolism, Montreal, 2008.
19. Maupetit-Mehouas S, Carel JC, Kottler ML, Linglart A: Progressive PTH resistance in pseudohypoparathyroidism (PHP) type 1a and 1b. European Society of Pediatric Endocrinology meeting, Istanbul, 2008.
20. Balavoine AS, Ladsous M, Velayoudom FL, Vlaeminck V, Cardot-Bauters C, d'Herbomez M, Wemeau JL: Hypothyroidism in patients with pseudohypoparathyroidism type Ia: clinical evidence of resistance to TSH and TRH. Eur J Endocrinol 2008; 159: 431-437.
21. Vlaeminck-Guillem V, d'Herbomez M, Pigny P, Fayard A, Bauters C, Decoulx M, Wemeau JL: Pseudohypoparathyroidism Ia and hypercalcitoninemia. J Clin Endocrinol Metab 2001; 86: 3091-3096.
22. Feng S, Ferlin A, Truong A, Bathgate R, Wade JD, Corbett S, Han S, Tannour-Louet M, Lamb DJ, Foresta C, Agoulnik AI: INSL3/ RXFP2 signaling in testicular descent. Ann NY Acad Sci 2009; 1160: 197-204.
23. Herman-Giddens ME, Slora EJ, Wasserman RC, Bourdony CJ, Bhapkar MV, Koch GG, Hasemeier CM: Secondary sexual characteristics and menses in young girls seen in office practice: a study from the pediatric research in office settings network. Pediatrics 1997; 99: 505-512.
24. Namnoum AB, Merriam GR, Moses AM, Levine MA: Reproductive dysfunction in women with Albright's hereditary osteodystrophy. J Clin Endocrinol Metab 1998; 83: 824-829.
25. Linglart A, Carel JC, Garabedian M, Le T, Mallet E, Kottler ML: GNAS1 lesions in pseudohypoparathyroidism Ia and Ic: genotype phenotype relationship and evidence of the maternal transmission of the hormonal resistance. J Clin Endocrinol Metab 2002; 87: 189-197.
26. Klopocki E, Hennig BP, Dathe K, Koll R, de Ravel T, Baten E, Blom E, Gillerot Y, Weigel JF, Kruger G, Hiort O, Seemann P, Mundlos S: Deletion and point mutations of PTHLH cause brachydactyly type E. Am J Hum Genet 2010; 86: 434-439.
27. Long DN, Levine MA, Germain-Lee EL: Bone mineral density in pseudohypoparathyroidism type 1a. J Clin Endocrinol Metab 2010; 95: 4465-4475.
28. Linglart A: Consequences of PTH resistance on adult bone. Arch Pediatr 2007; 14: 546-548.
29. Long DN, McGuire S, Levine MA, Weinstein LS, Germain-Lee EL: Body mass index differences in pseudohypoparathyroidism type 1a versus pseudopseudo hypoparathyroidism m a y implicate paternal imprinting of Galpha(s) in the development of human obesity. J Clin Endocrinol Metab 2007; 92: 1073-1079.
30. Mantovani G, Maghnie M, Weber G, De Menis E, Brunelli V, Cappa M, Loli P, Beck- Peccoz P, Spada A: Growth hormone-releasing hormone resistance in pseudohypoparathyroidism type Ia: new evidence for imprinting of the Gs alpha gene. J Clin Endocrinol Metab 2003; 88: 4070-4074.
31. Kaplan FS, Shore EM: Progressive osseous heteroplasia. J Bone Miner Res 2000; 15: 2084-2094.
32. Mouallem M, Shaharabany M, Weintrob N, Shalitin S, Nagelberg N, Shapira H, Zadik Z, Farfel Z: Cognitive impairment is prevalent in pseudohypoparathyroidism type Ia, but not in pseudopseudohypoparathyroidism: possible cerebral imprinting of Gsalpha. Clin Endocrinol (Oxf) 2008; 68: 233-239.
33. Carel JC, Le Stunff C, Condamine L, Mallet E, Chaussain JL, Adnot P, Garabedian M, Bougneres P: Resistance to the lipolytic action of epinephrine: a new feature of protein Gs deficiency. J Clin Endocrinol Metab 1999; 84: 4127-4131.
34. Wang HY, Watkins DC, Malbon CC: Antisense oligodeoxynucleotides to Gs protein alpha-subunit sequence accelerate differentiation of fibroblasts to adipocytes. Nature 1992; 358: 334-337.
35. Weinstein LS, Xie T, Qasem A, Wang J, Chen M: The role of GNAS and other imprinted genes in the development of obesity. Int J Obes (Lond) 2010; 34: 6-17.
36. Plagge A, Gordon E, Dean W, Boiani R, Cinti S, Peters J, Kelsey G: The imprinted signaling protein XL α s is required for postnatal adaptation to feeding. Nat Genet 2004; 36: 818-826.
37. Williams SR, Aldred MA, Der Kaloustian VM, Halal F, Gowans G, McLeod DR, Zondag S, Toriello HV, Magenis RE, Elsea SH: Haploinsufficiency of HDAC4 causes brachydactyly mental retardation syndrome, with brachydactyly type E, developmental delays, and behavioral problems. Am J Hum Genet 2010; 87: 219-228.
38. Ellsworth R, Howard JE: Studies on the physiology of the parathyroid glands. 6. Some responses of normal human kidneys and blood to intravenous parathyroid extract. Bull Johns Hopkins Hosp 1934; 55: 296.
39. Thiele S, de Sanctis L, Werner R, Grotzinger J, Aydin C, Juppner H, Bastepe M, Hiort O: Functional characterization of GNAS mutations found in patients with pseudohypoparathyroidism type Ic defines a new subgroup of pseudohypoparathyroidism affecting selectively Gsalpha-receptor interaction. Hum Mutat 2011; 32: 653-660.
40. Thiele S, Werner R, Ahrens W, Hoppe U, Marschke C, Staedt P, Hiort O: A disruptive mutation in exon 3 of the GNAS gene with Albright hereditary osteodystrophy, normocalcemic pseudohypoparathyroidism, and selective long transcript variant Gsalpha-l deficiency. J Clin Endocrinol Metab 2007; 92: 1764-1768.
41. de Nanclares GP, Fernandez-Rebollo E, Santin I, Garcia-Cuartero B, Gaztambide S, Menendez E, Morales MJ, Pombo M, Bilbao JR, Barros F, Zazo N, Ahrens W, Juppner H, Hiort O, Castano L, Bastepe M: Epigenetic defects of GNAS in patients with pseudohypoparathyroidism and mild features of Albright's hereditary osteodystrophy. J Clin Endocrinol Metab 2007; 92: 2370-2373.
42. Mariot V, Maupetit-Mehouas S, Sinding C, Kottler ML, Linglart A: A maternal epimutation of GNAS leads to Albright osteodystrophy and parathyroid hormone resistance. J Clin Endocrinol Metab 2008; 93: 661-665.
43. Mantovani G, de Sanctis L, Barbieri AM, Elli FM, Bollati V, Vaira V, Labarile P, Bondioni S, Peverelli E, Lania AG, Beck-Peccoz P, Spada A: Pseudohypoparathyroidism and GNAS epigenetic defects: clinical evaluation of Albright hereditary osteodystrophy and molecular analysis in 40 patients. J Clin Endocrinol Metab 2010; 95: 651-658.
44. Lebrun M, Richard N, Abeguile G, David A, Coeslier Dieux A, Journel H, Lacombe D, Pinto G, Odent S, Salles JP, Taieb A, Gandon- Laloum S, Kottler ML: Progressive osseous heteroplasia: a model for the imprinting effects of GNAS inactivating mutations in humans. J Clin Endocrinol Metab 2010; 95: 3028-3038.
45. Shore EM, Ahn J, Jan de Beur S, Li M, Xu M, Gardner RJ, Zasloff MA, Whyte MP, Levine MA, Kaplan FS: Paternally inherited inactivating mutations of the GNAS1 gene in progressive osseous heteroplasia. N Engl J Med 2002; 346: 99-106.
46. Linglart A, Bastepe M, Juppner H: Similar clinical and laboratory findings in patients with symptomatic autosomal dominant and spora dic pseudohypoparathyroidism type Ib despite different epigenetic changes at the GNAS locus. Clin Endocrinol (Oxf) 2007; 67: 822-831.
47. Linglart A, Gensure RC, Olney RC, Juppner H, Bastepe M: A novel STX16 deletion in autosomal dominant pseudohypoparathyroidism type Ib redefines the boundaries of a cisacting imprinting control element of GNAS. Am J Hum Genet 2005; 276: 804-814.
48. Sanchez J, Perera E, Jan de Beur S, Ding C, Dang A, Berkovitz GD, Levine MA: Madelung- like deformity in pseudohypoparathyroidism type 1b. J Clin Endocrinol Metab 2011; 96:E1507-E1511.
49. Mahmud FH, Linglart A, Bastepe M, Juppner H, Lteif AN: Molecular diagnosis of pseudohypoparathyroidism type Ib in a family with presumed paroxysmal dyskinesia. Pediatrics 2005; 115:e242-e244.
50. Burnstein MI, Kottamasu SR, Pettifor JM, Sochett E, Ellis BI, Frame B: Metabolic bone disease in pseudohypoparathyroidism: radiologic features. Radiology 1985; 155: 351-356.
51. Germain-Lee EL, Ding CL, Deng Z, Crane JL, Saji M, Ringel MD, Levine MA: Paternal imprinting of Galpha(s) in the human thyroid as the basis of TSH resistance in pseudohypoparathyroidism type 1a. Biochem Biophys Res Commun 2002; 296: 67-72.
52. Mantovani G, Bondioni S, Linglart A, Maghnie M, Cisternino M, Corbetta S, Lania AG, Beck-Peccoz P, Spada A: Genetic analysis and evaluation of resistance to thyrotropin and growth hormone-releasing hormone in pseudohypoparathyroidism type Ib. J Clin Endocrinol Metab 2007; 92: 3738-3742.
53. Maupetit-Mehouas S, Mariot V, Reynes C, Bertrand G, Feillet F, Carel JC, Simon D, Bihan H, Gajdos V, Devouge E, Shenoy S, Agbo- Kpati P, Ronan A, Naud-Saudreau C, Lienhardt A, Silve C, Linglart A: Quantification of the methylation at the GNAS locus identifies subtypes of sporadic pseudohypoparathyroidism type Ib. J Med Genet 2011; 48: 55-63.
54. Dixit A, Chandler KE, Lever M, Poole RL, Bullman H, Mughal MZ, Steggall M, Suri M: Pseudohypoparathyroidism type 1b due to paternal uniparental disomy of chromosome 20q. J Clin Endocrinol Metab 2013; 98:E103-E108.
55. Fernandez-Rebollo E, Lecumberri B, Garin I, Arroyo J, Bernal-Chico A, Goni F, Orduna R, Castano L, de Nanclares GP: New mechanisms involved in paternal 20q disomy associated with pseudohypoparathyroidism. Eur J Endocrinol 2010; 163: 953-962.
56. Bastepe M, Lane AH, Juppner H: Paternal uniparental isodisomy of chromosome 20q (patUPD20q)-and the resulting changes in GNAS1 methylation-as a plausible cause of pseudohypoparathyroidism. Am J Hum Genet 2001; 68: 1283-1289.
57. Heaney RP, Barger-Lux MJ, Dowell MS, Chen TC, Holick MF: Calcium absorptive effects of vitamin D and its major metabolites. J Clin Endocrinol Metab 1997; 82: 4111-4116.
58. Mantovani G, Ferrante E, Giavoli C, Linglart A, Cappa M, Cisternino M, Maghnie M, Ghizzoni L, de Sanctis L, Lania AG, Beck-Peccoz P, Spada A: Recombinant human GH replacement therapy in children with pseudohypoparathyroidism type Ia: first study on the effect on growth. J Clin Endocrinol Metab 2010; 95: 5011-5017.
59. Macfarlane RJ, Ng BH, Gamie Z, El Masry MA, Velonis S, Schizas C, Tsiridis E: Pharmacological treatment of heterotopic ossification following hip and acetabular surgery. Expert Opin Pharmacother 2008; 9: 767-786.
60. Al-Salameh A, Despert F, Kottler ML, Linglart A, Carel JC, Lecomte P: Resistance to epinephrine and hypersensitivity (hyperresponsiveness) to CB1 antagonists in a patient with pseudohypoparathyroidism type Ic. Eur J Endocrinol 2010; 162: 819-824.
61. Lietman SA, Goldfarb J, Desai N, Levine MA: Preimplantation genetic diagnosis for severe Albright hereditary osteodystrophy. J Clin Endocrinol Metab 2008; 93: 901-904.
62. De Groot L, Abalovich M, Alexander EK, Amino N, Barbour L, Cobin RH, Eastman CJ, Lazarus JH, Luton D, Mandel SJ, Mestman J, Rovet J, Sullivan S: Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2012; 97: 2543-2565.
63. LaFranchi SH: Approach to the diagnosis and treatment of neonatal hypothyroidism. J Clin Endocrinol Metab 2011; 96: 2959-2967.
64. Wu WI, Schwindinger WF, Aparicio LF, Levine MA: Selective resistance to parathyroid hormone caused by a novel uncoupling mutation in the carboxyl terminus of Gαs: a cause of pseudohypoparathyroidism type Ib. J Biol Chem 2001; 276: 165-171.
65. Zazo C, Thiele S, Martin C, Fernandez-Rebollo E, Martinez-Indart L, Werner R, Garin I, Hiort O, Perez de Nanclares G: Gsalpha activity is reduced in erythrocyte membranes of patients with psedohypoparathyroidism due to epigenetic alterations at the GNAS locus. J Bone Miner Res 2011; 26: 1864-1870.