GNAS mutations in pseudohypoparathyroidism type 1a and related disorders

Human Mutation

Volumn 36, Issue 1, 2015, Pages 11-19

  Lemos, Manuel C ^a   Thakker, Rajesh V ^b  

^a UNIVERSITY OF BEIRA INTERIOR   (Portugal)

^b UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

Albright hereditary osteodystrophy; GNAS; Gs alpha; Progressive osseous heteroplasia; Pseudohypoparathyroidism; Pseudopseudohypoparathyroidism

Indexed keywords

GNAS PROTEIN, HUMAN; STIMULATORY GUANINE NUCLEOTIDE BINDING PROTEIN;

ANIMAL; GENETIC ASSOCIATION; GENETIC PREDISPOSITION; GENETICS; GENOME IMPRINTING; HETEROTOPIC OSSIFICATION; HUMAN; METABOLIC BONE DISEASE; MUTATION; PSEUDOHYPOPARATHYROIDISM; SKIN DISEASE;

ANIMALS; BONE DISEASES, METABOLIC; GENETIC ASSOCIATION STUDIES; GENETIC PREDISPOSITION TO DISEASE; GENOMIC IMPRINTING; GTP-BINDING PROTEIN ALPHA SUBUNITS, GS; HUMANS; MUTATION; OSSIFICATION, HETEROTOPIC; PSEUDOHYPOPARATHYROIDISM; SKIN DISEASES, GENETIC;

EID: 84920091884     PISSN: 10597794     EISSN: 10981004     Source Type: Journal    
DOI: 10.1002/humu.22696     Document Type: Article

References (71)

1. Adegbite NS, Xu M, Kaplan FS, Shore EM, Pignolo RJ. 2008. Diagnostic and mutational spectrum of progressive osseous heteroplasia (POH) and other forms of GNAS-based heterotopic ossification. Am J Med Genet A 146A:1788-1796.
2. Ahrens W, Hiort O, Staedt P, Kirschner T, Marschke C, Kruse K. 2001. Analysis of the GNAS1 gene in Albright's hereditary osteodystrophy. J Clin Endocrinol Metab 86:4630-4634.
3. Akin L, Kurtoglu S, Yildiz A, Akin MA, Kendirici M. 2010. Vitamin D deficiency rickets mimicking pseudohypoparathyroidism. J Clin Res Pediatr Endocrinol 2:173-175.
4. Aldred MA, Trembath RC. 2000. Activating and inactivating mutations in the human GNAS1 gene. Hum Mutat 16:183-189.
5. Bartolomucci A, Possenti R, Mahata SK, Fischer-Colbrie R, Loh YP, Salton SR. 2011. The extended granin family: structure, function, and biomedical implications. Endocr Rev 32:755-797.
6. Bastepe M. 2012. Relative functions of Galphas and its extra-large variant XLalphas in the endocrine system. Horm Metab Res 44:732-740.
7. Bastepe M, Altug-Teber O, Agarwal C, Oberfield SE, Bonin M, Juppner H. 2011. Paternal uniparental isodisomy of the entire chromosome 20 as a molecular cause of pseudohypoparathyroidism type Ib (PHP-Ib). Bone 48:659-662.
8. Bastepe M, Frohlich LF, Hendy GN, Indridason OS, Josse RG, Koshiyama H, Korkko J, Nakamoto JM, Rosenbloom AL, Slyper AH, Sugimoto T, Tsatsoulis A, et al. 2003. Autosomal dominant pseudohypoparathyroidism type Ib is associated with a heterozygous microdeletion that likely disrupts a putative imprinting control element of GNAS. J Clin Invest 112:1255-1263.
9. Bastepe M, Frohlich LF, Linglart A, Abu-Zahra HS, Tojo K, Ward LM, Juppner H. 2005a. Deletion of the NESP55 differentially methylated region causes loss of maternal GNAS imprints and pseudohypoparathyroidism type Ib. Nat Genet 37:25-27.
10. Bastepe M, Juppner H. 2005b. GNAS locus and pseudohypoparathyroidism. Horm Res 63:65-74.
11. Cairns DM, Pignolo RJ, Uchimura T, Brennan TA, Lindborg CM, Xu M, Kaplan FS, Shore EM, Zeng L. 2013. Somitic disruption of GNAS in chick embryos mimics progressive osseous heteroplasia. J Clin Invest 123:3624-3633.
12. Castrop H, Oppermann M, Mizel D, Huang Y, Faulhaber-Walter R, Weiss Y, Weinstein LS, Chen M, Germain S, Lu H, Ragland D, Schimel DM, et al. 2007. Skeletal abnormalities and extra-skeletal ossification in mice with restricted Gsalpha deletion caused by a renin promoter-Cre transgene. Cell Tissue Res 330:487-501.
13. Chan I, Hamada T, Hardman C, McGrath JA, Child FJ. 2004. Progressive osseous heteroplasia resulting from a new mutation in the GNAS1 gene. Clin Exp Dermatol 29:77-80.
14. Cheeseman MT, Vowell K, Hough TA, Jones L, Pathak P, Tyrer HE, Kelly M, Cox R, Warren MV, Peters J. 2012. A mouse model for osseous heteroplasia. PLoS One 7:e51835.
15. Chen M, Gavrilova O, Liu J, Xie T, Deng C, Nguyen AT, Nackers LM, Lorenzo J, Shen L, Weinstein LS. 2005. Alternative Gnas gene products have opposite effects on glucose and lipid metabolism. Proc Natl Acad Sci USA 102:7386-7391.
16. Chillambhi S, Turan S, Hwang DY, Chen HC, Juppner H, Bastepe M. 2010. Deletion of the noncoding GNAS antisense transcript causes pseudohypoparathyroidism type Ib and biparental defects of GNAS methylation in cis. J Clin Endocrinol Metab 95:3993-4002.
17. Davies SJ, Hughes HE. 1993. Imprinting in Albright's hereditary osteodystrophy. J Med Genet 30:101-103.
18. De Sanctis L, Romagnolo D, Olivero M, Buzi F, Maghnie M, Scire G, Crino A, Baroncelli GI, Salerno M, Di Maio S, Cappa M, Grosso S, et al. 2003. Molecular analysis of the GNAS1 gene for the correct diagnosis of Albright hereditary osteodystrophy and pseudohypoparathyroidism. Pediatr Res 53:749-755.
19. den Dunnen JT, Antonarakis SE. 2001. Nomenclature for the description of human sequence variations. Hum Genet 109:121-124.
20. Dixit A, Chandler KE, Lever M, Poole RL, Bullman H, Mughal MZ, Steggall M, Suri M. 2013. Pseudohypoparathyroidism type 1b due to paternal uniparental disomy of chromosome 20q. J Clin Endocrinol Metab 98:E103-E108.
21. Elli FM, Barbieri AM, Bordogna P, Ferrari P, Bufo R, Ferrante E, Giardino E, Beck-Peccoz P, Spada A, Mantovani G. 2013a. Screening for GNAS genetic and epigenetic alterations in progressive osseous heteroplasia: first Italian series. Bone 56:276-280.
22. Elli FM, de Sanctis L, Bollati V, Tarantini L, Filopanti M, Barbieri AM, Peverelli E, Beck-Peccoz P, Spada A, Mantovani G. 2014a. Quantitative analysis of methylation defects and correlation with clinical characteristics in patients with pseudohypoparathyroidism type I and GNAS epigenetic alterations. J Clin Endocrinol Metab 99:E508-E517.
23. Elli FM, deSanctis L, Ceoloni B, Barbieri AM, Bordogna P, Beck-Peccoz P, Spada A, Mantovani G. 2013b. Pseudohypoparathyroidism type Ia and pseudo-pseudohypoparathyroidism: the growing spectrum of GNAS inactivating mutations. Hum Mutat 34:411-416.
24. Elli FM, de Sanctis L, Peverelli E, Bordogna P, Pivetta B, Miolo G, Beck-Peccoz P, Spada A, Mantovani G. 2014b. Autosomal dominant pseudohypoparathyroidism type Ib: a novel inherited deletion ablating STX16 causes loss of imprinting at the A/B DMR. J Clin Endocrinol Metab 99:E724-E728.
25. Fernandez-Rebollo E, Lecumberri B, Garin I, Arroyo J, Bernal-Chico A, Goni F, Orduna R, Castano L, de Nanclares GP. 2010. New mechanisms involved in paternal 20q disomy associated with pseudohypoparathyroidism. Eur J Endocrinol 163:953-962.
26. Fernandez-Rebollo E, Lecumberri B, Gaztambide S, Martinez-Indart L, Perez de Nanclares G, Castano L. 2013. Endocrine profile and phenotype-(epi)genotype correlation in Spanish patients with pseudohypoparathyroidism. J Clin Endocrinol Metab 98:E996-1006.
27. Fernandez-Rebollo E, Maeda A, Reyes M, Turan S, Frohlich LF, Plagge A, Kelsey G, Juppner H, Bastepe M. 2012. Loss of XLalphas (extra-large alphas) imprinting results in early postnatal hypoglycemia and lethality in a mouse model of pseudohypoparathyroidism Ib. Proc Natl Acad Sci USA 109:6638-6643.
28. Frohlich LF, Mrakovcic M, Steinborn R, Chung UI, Bastepe M, Juppner H. 2010. Targeted deletion of the Nesp55 DMR defines another Gnas imprinting control region and provides a mouse model of autosomal dominant PHP-Ib. Proc Natl Acad Sci USA 107:9275-9280.
29. Germain-Lee EL, Schwindinger W, Crane JL, Zewdu R, Zweifel LS, Wand G, Huso DL, Saji M, Ringel MD, Levine MA. 2005. A mouse model of Albright hereditary osteodystrophy generated by targeted disruption of exon 1 of the Gnas gene. Endocrinology 146:4697-4709.
30. Huh JY, Kwon MJ, Seo KY, Kim MK, Chae KY, Kim SH, Ki CS, Yoon MS, Kim DH. 2014. Novel nonsense GNAS mutation in a 14-month-old boy with plate-like osteoma cutis and medulloblastoma. J Dermatol 41:319-321.
31. Huso DL, Edie S, Levine MA, Schwindinger W, Wang Y, Juppner H, Germain-Lee EL. 2011. Heterotopic ossifications in a mouse model of Albright hereditary osteodystrophy. PLoS One 6:e21755.
32. Izzi B, Van Geet C, Freson K. 2012. Recent advances in GNAS epigenetic research of pseudohypoparathyroidism. Curr Mol Med 12:566-573.
33. Kervestin S, Jacobson A. 2012. NMD: a multifaceted response to premature translational termination. Nat Rev Mol Cell Biol 13:700-712.
34. Kozasa T, Itoh H, Tsukamoto T, Kaziro Y. 1988. Isolation and characterization of the human Gs alpha gene. Proc Natl Acad Sci USA 85:2081-2085.
35. 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, et al. 2010. Progressive osseous heteroplasia: a model for the imprinting effects of GNAS inactivating mutations in humans. J Clin Endocrinol Metab 95:3028-3038.
36. Linglart A, Carel JC, Garabedian M, Le T, Mallet E, Kottler ML. 2002. GNAS1 lesions in pseudohypoparathyroidism Ia and Ic: genotype phenotype relationship and evidence of the maternal transmission of the hormonal resistance. J Clin Endocrinol Metab 87:189-197.
37. Linglart A, Gensure RC, Olney RC, Juppner H, Bastepe M. 2005. A novel STX16 deletion in autosomal dominant pseudohypoparathyroidism type Ib redefines the boundaries of a cis-acting imprinting control element of GNAS. Am J Hum Genet 76:804-814.
38. Linglart A, Maupetit-Mehouas S, Silve C. 2013. GNAS-related loss-of-function disorders and the role of imprinting. Horm Res Paediatr 79:119-129.
39. Linglart A, Menguy C, Couvineau A, Auzan C, Gunes Y, Cancel M, Motte E, Pinto G, Chanson P, Bougneres P, Clauser E, Silve C. 2011. Recurrent PRKAR1A mutation in acrodysostosis with hormone resistance. N Engl J Med 364:2218-2226.
40. Liu J, Chen M, Deng C, Bourc'his D, Nealon JG, Erlichman B, Bestor TH, Weinstein LS. 2005. Identification of the control region for tissue-specific imprinting of the stimulatory G protein alpha-subunit. Proc Natl Acad Sci USA 102:5513-5518.
41. Mantovani G. 2011. Clinical review: pseudohypoparathyroidism: diagnosis and treatment. J Clin Endocrinol Metab 96:3020-3030.
42. Mantovani G, Bondioni S, Locatelli M, Pedroni C, Lania AG, Ferrante E, Filopanti M, Beck-Peccoz P, Spada A. 2004. Biallelic expression of the Gsalpha gene in human bone and adipose tissue. J Clin Endocrinol Metab 89:6316-6319.
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. 2010. Pseudohypoparathyroidism and GNAS epigenetic defects: clinical evaluation of Albright hereditary osteodystrophy and molecular analysis in 40 patients. J Clin Endocrinol Metab 95:651-658.
44. Mantovani G, Spada A. 2006. Mutations in the Gs alpha gene causing hormone resistance. Best Pract Res Clin Endocrinol Metab 20:501-513.
45. 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, et al. 2012. Exome sequencing identifies PDE4D mutations as another cause of acrodysostosis. Am J Hum Genet 90:740-745.
46. Novotny J, Svoboda P. 1998. The long (Gs(alpha)-L) and short (Gs(alpha)-S) variants of the stimulatory guanine nucleotide-binding protein. Do they behave in an identical way? J Mol Endocrinol 20:163-173.
47. Patten JL, Johns DR, Valle D, Eil C, Gruppuso PA, Steele G, Smallwood PM, Levine MA. 1990. Mutation in the gene encoding the stimulatory G protein of adenylate cyclase in Albright's hereditary osteodystrophy. N Engl J Med 322:1412-1419.
48. Plagge A, Gordon E, Dean W, Boiani R, Cinti S, Peters J, Kelsey G. 2004. The imprinted signaling protein XLalphas is required for postnatal adaptation to feeding. Nat Genet 36:818-826.
49. Plagge A, Kelsey G, Germain-Lee EL. 2008. Physiological functions of the imprinted Gnas locus and its protein variants Galpha(s) and XLalpha(s) in human and mouse. J Endocrinol 196:193-214.
50. Puzhko S, Goodyer CG, Kerachian MA, Canaff L, Misra M, Juppner H, Bastepe M, Hendy GN. 2011. Parathyroid hormone signaling via Galphas is selectively inhibited by an NH(2)-terminally truncated Galphas: implications for pseudohypoparathyroidism. J Bone Miner Res 26:2473-2485.
51. Regard JB, Malhotra D, Gvozdenovic-Jeremic J, Josey M, Chen M, Weinstein LS, Lu J, Shore EM, Kaplan FS, Yang Y. 2013. Activation of Hedgehog signaling by loss of GNAS causes heterotopic ossification. Nat Med 19:1505-1512.
52. Richard N, Abeguile G, Coudray N, Mittre H, Gruchy N, Andrieux J, Cathebras P, Kottler ML. 2012. A new deletion ablating NESP55 causes loss of maternal imprint of A/B GNAS and autosomal dominant pseudohypoparathyroidism type Ib. J Clin Endocrinol Metab 97:E863-E867.
53. Richard N, Molin A, Coudray N, Rault-Guillaume P, Juppner H, Kottler ML. 2013. Paternal GNAS mutations lead to severe intrauterine growth retardation (IUGR) and provide evidence for a role of XLalphas in fetal development. J Clin Endocrinol Metab 98:E1549-E1556.
54. Ringel MD, Schwindinger WF, Levine MA. 1996. Clinical implications of genetic defects in G proteins. The molecular basis of McCune-Albright syndrome and Albright hereditary osteodystrophy. Medicine (Baltimore) 75:171-184.
55. Shore EM, Ahn J, Jan de Beur S, Li M, Xu M, Gardner RJ, Zasloff MA, Whyte MP, Levine MA, Kaplan FS. 2002. Paternally inherited inactivating mutations of the GNAS1 gene in progressive osseous heteroplasia. N Engl J Med 346:99-106.
56. Shore EM, Kaplan FS. 2010. Inherited human diseases of heterotopic bone formation. Nat Rev Rheumatol 6:518-527.
57. Skinner JA, Cattanach BM, Peters J. 2002. The imprinted oedematous-small mutation on mouse chromosome 2 identifies new roles for Gnas and Gnasxl in development. Genomics 80:373-375.
58. Sunyaev SR. 2012. Inferring causality and functional significance of human coding DNA variants. Hum Mol Genet 21:R10-R17.
59. nd edition. Oxford, UK: Oxford University Press. p 675-686.
60. Thiele S, de Sanctis L, Werner R, Grotzinger J, Aydin C, Juppner H, Bastepe M, Hiort O. 2011. 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 32:653-660.
61. Thiele S, Werner R, Ahrens W, Hoppe U, Marschke C, Staedt P, Hiort O. 2007. 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 92:1764-1768.
62. Thiele S, Werner R, Ahrens W, Hubner A, Hinkel KG, Hoppner W, Igl B, Hiort O. 2010. Selective deficiency of Gsalpha and the possible role of alternative gene products of GNAS in Albright hereditary osteodystrophy and pseudohypoparathyroidism type Ia. Exp Clin Endocrinol Diabetes 118:127-132.
63. Todorova-Koteva K, Wood K, Imam S, Jaume JC. 2012. Screening for parathyroid hormone resistance in patients with nonphenotypically evident pseudohypoparathyroidism. Endocr Pract 18:864-869.
64. Turan S, Bastepe M. 2013. The GNAS complex locus and human diseases associated with loss-of-function mutations or epimutations within this imprinted gene. Horm Res Paediatr 80:229-241.
65. Turan S, Fernandez-Rebollo E, Aydin C, Zoto T, Reyes M, Bounoutas G, Chen M, Weinstein LS, Erben RG, Marshansky V, Bastepe M. 2014. Postnatal establishment of allelic Galphas silencing as a plausible explanation for delayed onset of parathyroid hormone resistance owing to heterozygous Galphas disruption. J Bone Miner Res 29:749-760.
66. Weinstein LS, Liu J, Sakamoto A, Xie T, Chen M. 2004. Minireview: GNAS: normal and abnormal functions. Endocrinology 145:5459-5464.
67. Williamson CM, Ball ST, Nottingham WT, Skinner JA, Plagge A, Turner MD, Powles N, Hough T, Papworth D, Fraser WD, Maconochie M, Peters J. 2004. A cis-acting control region is required exclusively for the tissue-specific imprinting of Gnas. Nat Genet 36:894-899.
68. Wu WI, Schwindinger WF, Aparicio LF, Levine MA. 2001. Selective resistance to parathyroid hormone caused by a novel uncoupling mutation in the carboxyl terminus of Galpha(s). A cause of pseudohypoparathyroidism type Ib. J Biol Chem 276:165-171.
69. Xie T, Plagge A, Gavrilova O, Pack S, Jou W, Lai EW, Frontera M, Kelsey G, Weinstein LS. 2006. The alternative stimulatory G protein alpha-subunit XLalphas is a critical regulator of energy and glucose metabolism and sympathetic nerve activity in adult mice. J Biol Chem 281:18989-18999.
70. Yu S, Yu D, Hainline BE, Brener JL, Wilson KA, Wilson LC, Oude-Luttikhuis ME, Trembath RC, Weinstein LS. 1995. A deletion hot-spot in exon 7 of the Gs alpha gene (GNAS1) in patients with Albright hereditary osteodystrophy. Hum Mol Genet 4:2001-2002.
71. Yu S, Yu D, Lee E, Eckhaus M, Lee R, Corria Z, Accili D, Westphal H, Weinstein LS. 1998. Variable and tissue-specific hormone resistance in heterotrimeric Gs protein alpha-subunit (Gsalpha) knockout mice is due to tissue-specific imprinting of the Gsalpha gene. Proc Natl Acad Sci USA 95:8715-8720.