A homozygous [Cys25]PTH(1-84) mutation that impairs PTH/PTHrP receptor activation defines a novel form of hypoparathyroidism

Journal of Bone and Mineral Research

Volumn 30, Issue 10, 2015, Pages 1803-1813

  Lee, Sihoon ^a   Mannstadt, Michael ^b   Guo, Jun ^b   Kim, Seul Min ^a   Yi, Hyon Seung ^a   Khatri, Ashok ^b   Dean, Thomas ^b   Okazaki, Makoto ^b   Gardella, Thomas J ^b   Jüppner, Harald ^b  

^a Gachon University   (South Korea)

^b MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

idiopathic hypoparathyroidism; pseudohypoparathyroidism type IB; PTH(1 84) mutation

Indexed keywords

CALCITRIOL; CALCIUM CARBONATE; COLECALCIFEROL 24 HYDROXYLASE; CYCLIC AMP; MESSENGER RNA; PARATHYROID HORMONE; PARATHYROID HORMONE RECEPTOR 1; PARATHYROID HORMONE[1-34]; VANILLOID RECEPTOR 5; PARATHYROID HORMONE RELATED PROTEIN;

ADULT; AGED; ARTICLE; BINDING AFFINITY; CLINICAL ARTICLE; COS 7 CELL LINE; DNA METHYLATION; DRUG DOSE INCREASE; FEMALE; GENETIC COUNSELING; GENETIC TRANSFECTION; HETEROZYGOSITY; HOMOZYGOSITY; HUMAN; HYPERPHOSPHATEMIA; HYPOCALCEMIA; HYPOPHOSPHATEMIA; IDIOPATHIC HYPOPARATHYROIDISM; IMMUNOREACTIVITY; IN VITRO STUDY; MALE; MIDDLE AGED; MISSENSE MUTATION; OSTEOLYSIS; PARATHYROID HORMONE BLOOD LEVEL; PHOSPHATE EXCRETION; PSEUDOHYPOPARATHYROIDISM; VERY ELDERLY; AMINO ACID SUBSTITUTION; ANIMAL; CHLOROCEBUS AETHIOPS; COS CELL LINE; GENETICS; HOMOZYGOTE; HYPOPARATHYROIDISM; METABOLISM;

AMINO ACID SUBSTITUTION; ANIMALS; CERCOPITHECUS AETHIOPS; COS CELLS; HOMOZYGOTE; HUMANS; HYPOPARATHYROIDISM; MUTATION, MISSENSE; PARATHYROID HORMONE; PARATHYROID HORMONE-RELATED PROTEIN;

EID: 84942195071     PISSN: 08840431     EISSN: 15234681     Source Type: Journal    
DOI: 10.1002/jbmr.2532     Document Type: Article

References (66)

1. Brown EM, MacLeod RJ., Extracellular calcium sensing and extracellular calcium signaling. Physiol Rev. 2001; 81: 239-97.
2. Hannan FM, Nesbit MA, Zhang C, et al., Identification of 70 calcium-sensing receptor mutations in hyper- and hypo-calcaemic patients: evidence for clustering of extracellular domain mutations at calcium-binding sites. Hum Mol Genet. 2012; 21: 2768-78.
3. Tomar N, Gupta N, Goswami R., Calcium-sensing receptor autoantibodies and idiopathic hypoparathyroidism. J Clin Endocrinol Metab. 2013; 98: 3884-91.
4. Ding C, Buckingham B, Levine MA., Familial isolated hypoparathyroidism caused by a mutation in the gene for the transcription factor GCMB. J Clin Invest. 2001; 108: 1215-20.
5. Baumber L, Tufarelli C, Patel S, et al., Identification of a novel mutation disrupting the DNA binding activity of GCM2 in autosomal recessive familial isolated hypoparathyroidism. J Med Genet. 2005; 42: 443-8.
6. Thomee C, Schubert SW, Parma J, et al., GCMB mutation in familial isolated hypoparathyroidism with residual secretion of parathyroid hormone. J Clin Endocrinol Metab. 2005; 90: 2487-92.
7. Mannstadt M, Bertrand G, Muresan M, et al., Dominant-negative GCMB mutations cause an autosomal dominant form of hypoparathyroidism. J Clin Endocrinol Metab. 2008; 93: 3568-76.
8. Mirczuk SM, Bowl MR, Nesbit MA, et al., A missense glial cells missing homolog B (GCMB) mutation, Asn502His, causes autosomal dominant hypoparathyroidism. J Clin Endocrinol Metab. 2010; 95: 3512-6.
9. Tomar N, Bora H, Singh R, et al., Presence and significance of a R110W mutation in the DNA-binding domain of GCM2 gene in patients with isolated hypoparathyroidism and their family members. Eur J Endocrinol. 2010; 162: 407-21.
10. Yi HS, Eom YS, Park Ie B, et al., Identification and characterization of C106R, a novel mutation in the DNA-binding domain of GCMB, in a family with autosomal-dominant hypoparathyroidism. Clin Endocrinol (Oxf). 2012; 76: 625-33.
11. Nesbit MA, Hannan FM, Howles SA, et al., Mutations affecting G-protein subunit alpha11 in hypercalcemia and hypocalcemia. N Engl J Med. 2013; 368: 2476-86.
12. Mannstadt M, Harris M, Bravenboer B, et al., Germline mutations affecting Galpha11 in hypoparathyroidism. N Engl J Med. 2013; 368: 2532-4.
13. Li D, Opas EE, Tuluc F, et al., Autosomal dominant hypoparathyroidism caused by germline mutation in GN A11: phenotypic and molecular characterization. J Clin Endocrinol Metab. 2014; 99: E1774-83.
14. Arnold A, Horst SA, Gardella TJ, Baba H, Levine MA, Kronenberg HM., Mutation of the signal peptide-encoding region of the preproparathyroid hormone gene in familial isolated hypoparathyroidism. J Clin Invest. 1990; 86: 1084-7.
15. Parkinson D, Thakker R., A donor splice site mutation in the parathyroid hormone gene is associated with autosomal recessive hypoparathyroidism. Nat Genet. 1992; 1: 149-53.
16. Sunthornthepvarakul T, Churesigaew S, Ngowngarmratana S., A novel mutation of the signal peptide of the preproparathyroid hormone gene associated with autosomal recessive familial isolated hypoparathyroidism. J Clin Endocrinol Metab. 1999; 84: 3792-6.
17. Ertl DA, Stary S, Streubel B, Raimann A, Haeusler G., A novel homozygous mutation in the parathyroid hormone gene (PTH) in a girl with isolated hypoparathyroidism. Bone. 2012; 51: 629-32.
18. Jan de Beur S, Levine M., Pseudohypoparathyroidism: clinical, biochemical, and molecular features. In:, Bilezikian JP, Markus R, Levine MA, editors. The parathyroids: basic and clinical concepts. New York: Academic Press; 2001. p. 807-25.
19. Weinstein L, Yu S, Warner D, Liu J., Endocrine manifestations of stimulatory G protein alpha-subunit mutations and the role of genomic imprinting. Endocr Rev. 2001; 22: 675-705.
20. Bastepe M, Jüppner H., Pseudohypoparathyroidism, Albright's hereditary osteodystrophy, and progressive osseous heteroplasia: disorders caused by inactivating GNAS mutations. In:, DeGroot LJ, Jameson JL, editors. Endocrinology. 6th ed. Philadelphia, PA: W.B. Saunders Company; 2010. p. 1223-35.
21. Mantovani G., Clinical review: pseudohypoparathyroidism: diagnosis and treatment. J Clin Endocrinol Metab. 2011; 96: 3020-30.
22. 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.
23. Mantovani G, Ballare E, Giammona E, Beck-Peccoz P, Spada A., The gsalpha gene: predominant maternal origin of transcription in human thyroid gland and gonads. J Clin Endocrinol Metab. 2002; 87: 4736-40.
24. Turan S, Fernández-Rebollo E, Aydin C, et al., Postnatal establishment of allelic Gαs silencing as a plausible explanation for delayed onset of parathyroid hormone resistance owing to heterozygous galphas disruption. J Bone Miner Res. 2014; 29: 749-60.
25. Bastepe M, Fröhlich 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. J Clin Invest 2003; 112: 1255-63.
26. Linglart A, Gensure RC, Olney RC, Jüppner H, Bastepe M., 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. 2005; 76: 804-14.
27. Chillambhi S, Turan S, Hwang DY, Chen HC, Jüppner H, Bastepe M., Deletion of the noncoding GNAS antisense transcript causes pseudohypoparathyroidism type Ib and biparental defects of GNAS methylation in cis. J Clin Endocrinol Metab. 2010; 95: 3993-4002.
28. Jin HY, Lee BH, Choi JH, et al., Clinical characterization and identification of two novel mutations of the GNAS gene in patients with pseudohypoparathyroidism and pseudopseudohypoparathyroidism. Clin Endocrinol (Oxf). 2011; 75: 207-13.
29. Sanchez J, Perera E, Jan de Beur S, et al., Madelung-like deformity in pseudohypoparathyroidism type 1b. J Clin Endocrinol Metab. 2011; 96: E1507-11.
30. Turan S, Ignatius J, Moilanen JS, et al., De novo STX16 deletions: an infrequent cause of pseudohypoparathyroidism type Ib that should be excluded in sporadic cases. J Clin Endocrinol Metab. 2012; 97: E2314-9.
31. Richard N, Abeguile G, Coudray N, et al., 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: E863-7.
32. Elli FM, de Sanctis L, Peverelli E, et al., Autosomal dominant pseudohypoparathyroidism type Ib: a novel inherited deletion ablating STX16 causes loss of imprinting at the A/B DMR. J Clin Endocrinol Metab. 2014: jc20133704.
33. Mantovani G, Bondioni S, Linglart A, et al., Genetic analysis and evaluation of resistance to thyrotropin and growth hormone-releasing hormone in pseudohypoparathyroidism type Ib. J Clin Endocrinol Metab. 2007; 92: 3738-42.
34. Linglart A, Bastepe M, Jüppner H., Similar clinical and laboratory findings in patients with symptomatic autosomal dominant and sporadic pseudohypoparathyroidism type Ib despite different epigenetic changes at the GNAS locus. Clin Endocrinol (Oxf). 2007; 67: 822-31.
35. Mantovani G, de Sanctis L, Barbieri AM, et al., Pseudohypoparathyroidism and GNAS epigenetic defects: clinical evaluation of Albright hereditary osteodystrophy and molecular analysis in 40 patients. J Clin Endocrinol Metab. 2010; 95: 651-8.
36. Fernández-Rebollo E, Pérez de Nanclares G, Lecumberri B, et al., Exclusion of the GNAS locus in PHP-Ib patients with broad GNAS methylation changes: evidence for an autosomal recessive form of PHP-Ib? J Bone Miner Res. 2011; 26: 1854-63.
37. Maupetit-Mehouas S, Mariot V, Reynes C, et al., Quantification of the methylation at the GNAS locus identifies subtypes of sporadic pseudohypoparathyroidism type Ib. J Med Genet. 2011; 48: 55-63.
38. Elli FM, de Sanctis L, Bollati V, et al., Quantitative analysis of methylation defects and correlation with clinical characteristics in patients with pseudohypoparathyroidism type I and GNAS epigenetic alterations. J Clin Endocrinol Metab. 2014; 99: E508-17.
39. Bastepe M, Lane AH, Jüppner 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: 1283-9.
40. Bastepe M, Altug-Teber O, Agarwal C, Oberfield SE, Bonin M, Jüppner H., Paternal uniparental isodisomy of the entire chromosome 20 as a molecular cause of pseudohypoparathyroidism type Ib (PHP-Ib). Bone. 2011; 48: 659-62.
41. Fernández-Rebollo E, Lecumberri B, Garin I, et al., New mechanisms involved in paternal 20q disomy associated with pseudohypoparathyroidism. Eur J Endocrinol. 2011; 163: 953-62.
42. Dixit A, Chandler KE, Lever M, et al., Pseudohypoparathyroidism type 1b due to paternal uniparental disomy of chromosome 20q. J Clin Endocrinol Metab. 2013; 98: E103-8.
43. Pérez de Nanclares G, Fernández-Rebollo E, Santin I, et al., Epigenetic defects of GNAS in patients with pseudohypoparathyroidism and mild features of Albright's hereditary osteodystrophy. J Clin Endocrinol Metab. 2007; 92: 2370-3.
44. Unluturk U, Harmanci A, Babaoglu M, et al., Molecular diagnosis and clinical characterization of pseudohypoparathyroidism type-Ib in a patient with mild Albright's hereditary osteodystrophy-like features, epileptic seizures, and defective renal handling of uric acid. Am J Med Sci. 2008; 336: 84-90.
45. 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: 661-5.
46. Yamamoto M, Takuwa Y, Masuko S, Ogata E., Effects of endogenous and exogenous parathyroid hormone on tubular reabsorption of calcium in pseudohypoparathyroidism. J Clin Endocrinol Metab. 1988; 66: 618-25.
47. Kruse K, Kracht U, Wohlfart K, Kruse U., Biochemical markers of bone turnover, intact serum parathyroid hormone and renal calcium excretion in patients with pseudohypoparathyroidism and hypoparathyroidism before and during vitamin D treatment. Eur J Pediatr. 1989; 148: 535-9.
48. Mitchell DM, Regan S, Cooley MR, et al., Long-term follow-up of patients with hypoparathyroidism. J Clin Endocrinol Metab. 2012; 97: 4507-14.
49. Shimizu M, Carter PH, Khatri A, Potts JT Jr, Gardella TJ., Enhanced activity in parathyroid hormone (1-14) and (1-11): novel peptides for probing the ligand-receptor interaction. Endocrinology. 2001; 142: 3068-74.
50. Salusky IB, Goodman WG, Kuizon BD, et al., Similar predictive value of bone turnover using first- and second-generation immunometric PTH assays in pediatric patients treated with peritoneal dialysis. Kidney Int. 2003; 63: 1801-8.
51. Tan K, Ong L, Sethi SK, Saw S., Comparison of the Elecsys PTH(1-84) assay with four contemporary second generation intact PTH assays and association with other biomarkers in chronic kidney disease patients. Clin Biochem. 2013; 46: 781-6.
52. Guo J, Song L, Liu M, et al., Activation of a non-cAMP/PKA signaling pathway downstream of the PTH/PTHrP receptor is essential for a sustained hypophosphatemic response to PTH infusion in male mice. Endocrinology. 2013; 154: 1680-9.
53. Cheloha RW, Maeda A, Dean T, Gardella TJ, Gellman SH., Backbone modification of a polypeptide drug alters duration of action in vivo. Nat Biotech. 2014; 32: 653-5.
54. Dean T, Khatri A, Potetinova Z, Willick GE, Gardella TJ., Role of amino acid side chains in region 17-31 of parathyroid hormone (PTH) in binding to the PTH receptor. J Biol Chem. 2006; 281: 32485-95.
55. Maeda A, Okazaki M, Baron DM, et al., Critical role of parathyroid hormone (PTH) receptor-1 phosphorylation in regulating acute responses to PTH. Proc Natl Acad Sci USA. 2013; 110: 5864-9.
56. Linglart A, Menguy C, Couvineau A, et al., Recurrent PRKAR1A mutation in acrodysostosis with hormone resistance. N Engl J Med. 2011; 364: 2218-26.
57. Biesecker LG, Mullikin JC, Facio FM, et al., The ClinSeq Project: piloting large-scale genome sequencing for research in genomic medicine. Genome Res. 2009; 19: 1665-74.
58. Pioszak AA, Parker NR, Gardella TJ, Xu HE,. Structural basis for parathyroid hormone-related protein binding to the parathyroid hormone receptor and design of conformation-selective peptides. J Biol Chem. 2009; 284: 28382-91.
59. Bouillon R, Coopmans W, Degroote D, Radoux D, Eliard P., Immunoradiometric assay of parathyrin with polyclonal and monoclonal region-specific antibodies. Clin Chem. 1990; 36: 271-6.
60. John M, Goodman W, Gao P, Cantor T, Salusky I, Jüppner H., A novel immunoradiometric assay detects full-length human PTH but not amino-terminally truncated fragments: implications for PTH measurements in renal failure. J Clin Endocrinol Metab. 1999; 84: 4287-90.
61. Fournier A, Solal M, Oprisiu R, et al., Optimal range of plasma concentration of true 1-84 parathyroid hormone in patients on maintenance dialysis. J Clin Endocrinol Metab. 2001; 86: 1840-2.
62. Couvineau A, Laburthe M., The family B1 GPCR: structural aspects and interaction with accessory proteins. Curr Drug Targets. 2012; 13: 103-15.
63. Vilardaga JP, Gardella TJ, Wehbi VL, Feinstein TN., Non-canonical signaling of the PTH receptor. Trends Pharmacol Sci. 2012; 33: 423-31.
64. Brown EM., Control of parathyroid hormone secretion by its key physiological regulators. In:, Bilezikian J, ed. The parathyroids: basic and clinical concepts. San Diego: Academic Press 2015. p. 101-18.
65. Au AY, McDonald K, Gill A, et al., PTH mutation with primary hyperparathyroidism and undetectable intact PTH. N Engl J Med. 2008; 359: 1184-6.
66. Hollenstein K, Kean J, Bortolato A, et al., Structure of class B GPCR corticotropin-releasing factor receptor 1. Nature. 2013; 499: 438-43.