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Molecular Analysis of the Thyroid Stimulating Hormone Receptor Gene in Unrelated Patients with Congenital Hypothyroidism

Maslinda Musa, and Fatimah Harun, and Sarni Mat Junit, (2007) Molecular Analysis of the Thyroid Stimulating Hormone Receptor Gene in Unrelated Patients with Congenital Hypothyroidism. Malaysian Journal of Biochemistry and Molecular Biology, 15 (1). pp. 8-18. ISSN ISSN 1511-2616

Full text not available from this repository.

Official URL: http://ejum.fsktm.um.edu.my/ArticleInformation.aspx?ArticleID=576

Affiliations

University of Malaya. Faculty of Medicine. Dept. of Molecular Medicine
University of Malaya. Faculty of Medicine.Dept. of Paediatrics

Abstract

We examined the thyroid stimulating hormone receptor (TSHR) gene in a series of 33 unrelated patients with congenital hypothyroidism (CH). Twelve of the patients had thyroid agenesis, one with thyroid ectopy, 18 with normal thyroid gland and two with unknown status of the thyroid gland. The entire coding region of the TSHR gene (exons 1 to 10) of these patients was PCRamplified and analysed using the single-stranded conformational polymorphism (SSCP) technique. Variations in SSCP banding patterns were detected in seven exons/fragments of the TSHR gene; exon 1, exon 6, exon 7, exon 8, exon 9, fragments 3 and 6 of exon 10. Subsequent DNA sequence analysis revealed the presence of eight polymorphisms, two of which were novel; IVS5- 31C>T and IVS9+3A>G. The other six polymorphisms; IVS6+13A>G, IVS7-25insTCTC, 253C>A (P52T), 561T>C (N187N), 1377G>A (A459A) and 2181C>G (D727E) have all been previously reported. Mutation in the TSHR gene that could be associated with CH phenotypes was not detected in all patients, indicating that the cause of the CH phenotypes was due to mutation in other thyroid-related genes.

Item Type:Journal
Keywords:Congenital hypothyroidism, TSH Receptor, PCR-SSCP, polymorphisms
Subjects:Q Science, Computer Science
R Medicine, Dentistry, Pharmacy, Nursing
ID Code:2180

1. Toublanc JE. Comparison of epidemiological data on congenital hypo-thyroidism in Europe with those of other parts in the world. Horm Res 1992; 138: 230-235.

2. Ridgway EC. Modern concepts of primary thyroid gland failure. Clin Chem 1996; 42:179-182.

3. van Vliet G. Development of the thyroid gland: lessons from congenitally hypothyroid mice and men. Clin Genet 2003; 63: 445-455.

4. Collu R, Tang J, Castagne J, Lagace G, Masson N, Huot C, Deal C, Delvin E, Faccenda E, Eidne KA, van Vliet G. A novel mechanism for isolated central hypothyroidism: inactivating mutations in the thyrotropin-releasing hormone receptor gene. J Clin Endocrinol Metab 1997; 82:1361-1365.

5. Heinrichs C, Parma J, Scherberg NH. Congenital central isolated hypothyroidism caused by a homozygous mutation in the TSH-beta subunit gene. Thyroid 2000; 10: 387-391.

6. Dubuis JM, Glorieux J, Richer F, Deal CL, Dussault JH, van Vliet G. Outcome of severe congenital hypothyroidism: closing the developmental gap with early high dose levothyroxine treatment. J Clin Endocrinol Metab 1996;81: 222-227.

7. van Vliet G. Neonatal hypothyroidism: treatment and outcome. Thyroid 1999; 9: 79-84

8. van Vliet G. Treatment of congenital hypothyroidism. Lancet 2001; 358: 86-87.

9. Pohlenz J, Dumitrescu A, Zundel D, Martine U, Schönberger W, Koo E, Weiss RE, Cohen RN, Kimura S, Refetoff S. Partial deficiency of thyroid transcription factor 1 produces predominantly neurological defects in humans and mice. J Clin Invest 2002; 109: 469-473.

10. Krude H, Schutz B, Biebermann H, von Moers A, Schnabel D, Neitzel H, Tonnies H, Weise D, Lafferty A, Schwarz S, DeFelice M, von Deimling A, van Landeghem F, DiLauro R, Gruters A. Choreoathetosis, hypothyroidism, and pulmonary alterations due to human NKX2-1 haploinsufficiency. J Clin Invest 2002; 109: 475-480.

11. Clifton-Bligh RJ, Wentworth JM, Heinz P, Crisp MS, John R, Lazarus JH, Ludgate M, Chatterjee K. Mutation of the gene encoding human TTF-2 associated with thyroid agenesis, cleft palate and choanal atresia. Nat Genet 1998;19: 399-401.

12. Castanet M, Park SM, Smith A, Bost M, Leger J, Lyonnet S, Pelet A, Czernichow P, Chatterjee K, Polak M. A novel loss-of-function mutation in TTF-2 is associated with congenital hypothyroidism, thyroid agenesis and cleft palate. Hum Molec Genet 2002; 11: 2051-2059.

13. Macchia PE, Lapi P, Krude H, Pirro TM, Missero C, Chiovato L, Souabni A, Baserga M, Tassi V, Pinchera A, Fenzi G, Gruters A, Busslinger M, Di Lauro R. PAX 8 mutations associated with congenital hypothyroidism caused by thyroid dysgenesis. Nat Genet 1998; 19: 83-86.

14. Congdon T, Nguyen LQ, Nogueira CR, Habiby RL, Medeiros-Neto G, Kopp P. A novel mutation (Q40P) in Pax8 associated with congenital hypothyroidism and thyroid hypoplasia: Evidence for phenotypic variability in mother and child. J Clin Endocrinol Metab 2001; 86: 3962-3967.

15. Meeus L, Gilbert B, Rydlewski C, Parma J, Roussie AL, Abramowicz M, Vilain C, Christophe D, Costagliola S, Vassart G. Characterization of a Novel Loss of Function Mutation of PAX8 in a Familial Case of Congenital hypothyroidism with In-Place, Normal-Sized Thyroid. J Clin Endocrinol Metab 2004; 89: 4285-4291.

16. Macchia PE. Recent advances in understanding the molecular basis of primary congenital hypothyroidism. Mol Med Today 2000; 6: 36-42.

17. Rousseau-Merck MF, Misrahi M, Loosfelt H, Atger M, Milgrom E, Berger R. Assignment of the human thyroid stimulating hormone receptor (TSHR) gene to chromosome 14q31. Genomics 1990; 8: 233-236.

18. Libert F, Lefort A, Gerard C, Parmentier M, Perret J, Ludgate M, Dumont JE., Vassart G. Cloning, sequencing and expression of the human thyrotropin (TSH) receptor: evidence for the binding of autoantibodies. Biochem Biophys Res Commun 1989; 165: 1250-1255.

19. Misrahi M, Loosfelt H, Atger M, Sar S, Guiochon-Mantel A, Milgrom E. Cloning, sequencing and expression of human TSH receptor. Biochem Biophys Res Commun 1990; 166: 394-403.

20. Gross B, Misrahi M, Sar S, Milgrom E. Composite structure of the human thyrotropin receptor gene. Biochem Biophys Res Commun 1991; 177: 679-687.

21. Lazzaro D, Price M, DeFelice M, DiLauro R. The transcription factor TTF-1 is expressed at the onset of thyroid and lung morphogenesis and in restricted regions of the foetal brain. Development 1991; 113: 1093-1104.

22. Brown RS, Shalhoub V, Coulter S, Alex S, Joris I, DeVito W, Lian J, Stein GS. Developmental regulation of thyrotropin receptor gene expression in the fetal and neonatal rat thyroid: relation to thyroid morphology and to thyroid-specific gene expression. Endocrinology 2000; 141:340-345.

23. Abramowicz MJ, Duprez L, Parma J, Vassart G, Heinrichs C. Familial congenital hypothyroidism due to inactivating mutation of the thyrotropin receptor causing profound hypoplasia of the thyroid gland. J Clin Invest 1997; 99: 3018-3024.

24. Kopp P. Perspective: Genetics defects in the etiology of congenital hypothyroidism. Endocrinology 2002; 143(6): 2019-2024.

25. Orita M, Suzuki Y, Sekiyu T, Hayashi K. Rapid and sensitive detection of point mutationns and DNA polymorphisms using the polymerase chain reaction. Genomics 1989; 5: 874-879.

26. Hongyo T, Buzard GS, Calvert RJ, Weghorst CS. Cold SSCP: a simple, rapid and non-radioactive method for optimized single-strand conformation polymorphism analyses. Nucl Acids Res 1993; 21: 3637-4642.

27. Hayashi K. PCR-SSCP: A method for detection of mutations. Genet Anal Tech Appl 1992; 9: 73-79.

28. Hayashi K, Yandell DW. How sensitive is PCR-SSCP? Hum Mut 1993; 2: 338-346.

29. Sheffield VC, Beck JC, Kwitek AE, Sandstrom DW, Stone EM. The sensitivity of single-strand conformation polymorphism analysis for the detection of single base substitutions. Genomics 1993; 16: 325-332.

30. Bohr URM, Behr M, Loos U. A heritable point mutation in an extracellular domain of the thyrotropin receptor in patients with Grave’s ophthalmopathy. J Clin Endocrinol Metab 1993; 78: 256-260.

31. Gabriel EM, Bergert ER, Grant CS, van Heerden JA, Thompson GB, Morris JC. Germ line polymorphism of codon 727 of human thyroid-stimulating hormone receptor is associated with toxic multinodular goiter. J Clin Endocrinol Metab 1999; 84: 3328-3335.

32. Haga H, Yamada R, Ohnishi Y, Nakamura Y, Tanaka T. Gene-based SNP discovery as a part of the Japanese Millenium Genome Project: identification of 190562 genetic variations in the human genome. J Hum Genet 2002; 47:605-610.

33. Murakami M, Mori M. Identification of immunogenic regions in human thyrotropin receptor for immunoglobulin G of patients with Grave’s disease. Biochem Biophys Res Commun 1990; 171: 512-518.

34. Nagayama Y, Wadsworth HL, Russo D, Chazenbalk GD, Rapoport B. Binding domains of stimulatory and inhibitory thyrotropin (TSH) receptor autoantibodies determined with chimeric TSH-lutropin /chorionic gonadotropin receptors. J Clin Invest 1991; 88: 336-340.

35. Kosugi S, Ban T, Akamizu T, Kohn LD. Identification of separate determinants on the thyrotropin receptor reactive with Graves’ thyroid stimulating antibodies and with thyroid stimulating blocking antibodies in idiopathic myxedema: These determinants have no homologous sequence on gonadotropin receptors. Mol Endocrinol 1992; 6: 168-180.

36. Nagayama Y, Rapoport B. The thyrothropin receptor 25 years after its discovery: new insight after its molecular cloning. Mol Endocrinol 1992; 6: 145-156.

37. Kosugi S, Ban T, Kohn LD. Identification of thyroid stimulating antibody-specific interaction sites in the Nterminal region of the thyrotropin receptor. Mol Endocrinol 1993; 7: 114-130.

38. Loos U, Hagner S, Bohr UR, Bogatkewitsch GS, Jakobs KH, van Koppen CJ. Enhanced cAMP accumulation by the human thyrotropin receptor variant with the Pro52Thr substitution in the extracellular domain. Eur J Biochem 1995; 232: 62-65.

39. Duprez L, Parma J, van Sande J, Rodien P, Dumont JE, Vassart G, Abramowicz M. TSH receptor mutations and thyroid diseases. Trends Endocrinol Metab 1998; 91: 133-140.

40. Tonacchera M, Pinchera A. Thyrotropin receptor polymorphisms and thyroid diseases. J Clin Endocrinol Metab 2000; 85: 2637-2639.

41. Watson PF, French A, Pickerill AP, McIntosh RS, Weetman AP. Lack of association between a polymorphism in the coding region of the thyrotropin receptor gene and Grave’s disease. J Clin Endocrinol Metab 1995; 80: 1032-1035.

42. Cuddihy RM, Bryant WP, Bahan R. Normal function in vivo of a homozygotic polymorphism in the human thyrotropin receptor. Thyroid 1995; 5: 255-257

43. Simanainen J, Kinch A, Westermark K, Winsa B, Bengtsson M, Schuppert F, Westermark B, Heldin N-E. Analysis of mutations in exon 1 of the human thyrotropin receptor gene: high frequency of the D36H and P52T polymorphic variants. Thyroid 1999; 9: 7-11.

44. Hiratani H, Bowden DW, Ikegami S, Shirasawa S, Shimizu A, Iwatani Y, Akamizu T. Multiple SNPs in intron 7 of thyrotrpoin receptor are associated with Grave’s disease. J Clin Endocrinol Metab 2005; 90: 2898-2903.

45. Nogueira CR, Kopp P, Arseven OK, Santos CLS, Jameson JL, Medeiros-Neto G. Thyrotropin receptor mutations in hyperfunctioning thyroid adenomas from Brazil. Thyroid 1999; 9: 1063-1068.

46. Muhlberg T, Herrmann K, Joba W, Kirchberger M, Heberling, HJ, Heufelder, AE. Lack of association of onautoimmune hyperfunctioning thyroid disorders and germline polymorphism of codon 727 of the human thyrotropin receptor in a European Caucasion population. J Clin Endocrinol Metab 2000; 85: 2640-2643.

47. Sykiotis G, Neumann S, Georgopoulos N, Sgourous A, Papachatzopoulou A, Markou K, Kyriazopoulou V, Pashke R, Vagenakis A, Papavassiliou A. Functional significance of the thyrotropin receptor germline polymorphism D727E. Biochem Biophys Res Commun 2003; 301: 1051-1056.

48. Biebermann H, Schoneberg T, Krude H, Schultz G, Gudermann T, Gruters A. Mutations of the human thyrotropin receptor gene causing thyroid hypoplasia and persistent congenital hypothyroidism. J Clin Endocrinol Metab 1997; 82: 3471-3480.

49. Sunthornthepvarakul T, Gottschalk ME, Hayashi Y, efetoff S. Brief report: resistance to thyrotropin caused by

mutations in the thyrotropin-receptor gene. N Engl J Med 1995; 332: 155-160.

50. Tiosano D, Pannain S, Vassart G, Parma J, Gershoni-Baruch R, Mandel H, Lotan R, Zaharan Y, Pery M, Weiss RE, Refetoff S, Hochberg Z. The hypothyroidism in an inbred kindred with congenital thyroid hormone and glucocorticoid deficiency is due to a mutation producing a truncated thyrotropin receptor. Thyroid 1999; 9: 887-894.

51. de Roux N, Misrahi M, Brauner R, Houang M, Carel JC, Granier M, Le Bouc Y, Ghinea N, Boumedienne A, Toublanc JE, Milgrom E. Four families with loss of function mutations of the thyrotropin receptor. J Clin Endocrinol Metab 1996; 81: 4229-4235.

52. Gagne N, Parma J, Deal C, Vassart G, van Vliet G. apparent congenital athyreosis contrasting with normal plasma thyroglobulin levels and associated with inactivating mutations in the thyrotropin receptor gene: are athyreosis and ectopic thyroid distinct entities? J Clin Endocrinol Metab 1998; 83: 1771-1775.

53. Jordan N, Williams N, Gregory JW, Evans C, Owen M, Ludgate M. The W546X mutation of the thyrotropin receptor gene: potential major contributor to thyroid dysfunction in a Caucasian population. J Clin Endocrinol Metab 2003; 88: 1002-1005.

54. Antonarakis SE. Recommendations for a nomenclature system for human gene mutations. Nomenclature Working Group. Hum Mutat 1998; 11: 1-3

55. Clifton-Bligh RJ, Gregory JW, Ludgate M, John R, Persani L, Asteria C, Beck-Peccoz P, Chatterjee VK. Two novel mutations in the thyrotropin (TSH) receptor gene in a child with resistance to TSH. J Clin Endocrinol Metab 1997; 82: 1094-1100.

56. Onigata K, Hattori S, Yamada S, Kowase T, Takano Y, Moriwaka A, Nishiyama S, Mizuno H. The R450H mutation of the thyrotropin receptor gene is common in Japanese patients with resistance to thyrotropin. Proc 75th Annual Meeting of the American Thyroid Association, Palm Beach, FL, (Abstract 061). Thyroid 2003; 13: 689.

57. Tonacchera M, Agretti P, Pinchera A, Rosellini V, Perri, Collecchi P, Vitti P, Chiovato L. Congenital hypothyroidism with impaired thyroid response to thyrotropin (TSH) and absent circulating thyroglobulin: evidence for a new inactivating mutation of the TSH receptor gene. J Clin Endocrinol Metab 2000; 85: 1001-1008.

58. Nagashima T, Murakami M, Onigata K, Morimura T, Nagashima K, Mori M, Morikawa A. Novel inactivating missense mutations in the thyrotropin receptor gene in Japanese children with resistance to thyrotropin. Thyroid 2001; 11: 551-559.

59. Alberti L, Proverbio MC, Costagliola S, Romoli R, Boldrighini B, Vigone MC, Weber G, Chiumello G, Beck-Peccoz P, Persani L. Germline mutations of TSH Receptor gene as a cause of nonautoimmune subclinical hypothyroidism J Clin Endocrinol Metab 2002; 87(6): 2549-2555

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