Clinical and Experimental Pediatrics

대한소아청소년과학회 (The Korean Pediatric Society)
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형제에서 발생한 갑상선 자극호르몬 수용체 유전자 돌연변이에 의한 갑상선 항진증 2례

Hyperthyroidism Caused by a Mutation in the Thyrotropin Receptor Gene in Two Brothers

  • 김재현 (서울대학교 의과대학 소아과학교실) ;
  • 이성수 (서울대학교 의과대학 소아과학교실) ;
  • 임중섭 (원자력병원 소아과) ;
  • 신충호 (서울대학교 의과대학 소아과학교실) ;
  • 양세원 (서울대학교 의과대학 소아과학교실)
  • Kim, Jae Hyun (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Lee, Sung Soo (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Lim, Jung Sup (Department of Pediatrics, Korea Cancer Center Hospital) ;
  • Shin, Choong Ho (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Yang, Sei Won (Department of Pediatrics, Seoul National University College of Medicine)
  • 투고 : 2004.09.02
  • 심사 : 2004.10.13
  • 발행 : 2005.03.15
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초록

선천성 갑상선 항진증은 드문 질환으로 모체로부터 TSH에 대한 자가항체가 태반을 통해 태아에게 전달되어 생기며 일시적인 경우가 많다. 선천성 갑상선 항진증이 지속되지만 자가면역질환의 검사 소견을 보이지 않을 때에는 TSHR의 돌연변이에 의한 갑상선 항진증을 고려해야 한다. 저자들은 TSHR의 돌연변이에 의한 갑상선 항진증 증례를 2례 경험하였기에 문헌고찰과 함께 보고하는 바이다.

Thyrotropin receptor(TSHR) mutations must be considered when congenital hyperthyroidism has persisted, but there has been no evidence for autoimmunity. TSHR mutations leading to constitutive activation of the thyroid gland were identified as the molecular cause of autosomal dominant nonautoimmune hyperthyroidism and sporadic congenital hyperthyroidism. We report two cases of hyperthyroidism caused by germline TSHR mutation who presented with exessive sweating and no evidence of autoimmune thyroid disease. They were brothers and their mother had undergone thyroidectomy because of hyperthyroidism. Direct sequencing of the polymerase chain reaction-amplified exon 10 of the TSHR genomic DNA revealed a transition of GCT to GTT, resulting in an exchange of alanine 627 to valine in the patients and their mother. This might be a novel mutation or polymorphism, but we did not perform any functional gene study. But considering the clinical profiles, we can conclude that hyperthyroidism of these two brothers might come from the point mutation described above.

키워드

참고문헌

  1. Sperling MA. Pediatric endocrinology. 2nd ed. Philadelphia : Saunders 2002:161-85
  2. Parma J, Duprez L, Van Sande J, Cochaux P, Gervy C, Mockel J, et al. Somatic mutations in the thyrotropin receptor gene cause hyperfunctioning thyroid adenomas. Nature 1993;365:649-51 https://doi.org/10.1038/365649a0
  3. Fuhrer D, Wonerow P, Willgerodt H, Paschke R. Identification of a new thyrotropin receptor germline mutation $(Leu^{629}Phe)$ in a family with neonatal onset of autosomal dominant nonautoimmune hyperthyroidism. J Clin Endocrinol Metab 1997;82:4234-8. https://doi.org/10.1210/jc.82.12.4234
  4. Thomas JS, Leclere J, Hartemann P, Duheille J, Orgiazzi J, Petersen M, et al. Familial hyperthyroidism without evidence of autoimmunity. Acta Endocrinol(Copenh) 1982;100:512-8
  5. Duprez L, Parma J, Van Sande J, Allgeier A, Leclere J, Schvartz C, et al. Germline mutations in the thyrotropin receptor gene cause non-autoimmune autosomal dominant hyperthyroidism. Nat Genet 1994;7:396-401. https://doi.org/10.1038/ng0794-396
  6. Kopp P, van Sande J, Parma J, Duprez L, Gerber H, Joss E, et al. Brief report: congenital hyperthyroidism caused by a mutation in the thyrotropin-receptor gene. N Engl J Med 1995;332:150-4 https://doi.org/10.1056/NEJM199501193320304
  7. De Roux N, Polak M, Couet J, Leger J, Czernichow P, Milgrom E, et al. A neomutation of the thyroid-stimulating hormone receptor in a severe neonatal hyperthyroidism. J Clin Endocrinol Metab 1996;81:2023-6 https://doi.org/10.1210/jc.81.6.2023
  8. Schwab KO, Gerlich M, Broecker M, Sohlemann P, Derwahl M, Lohse MJ. Constitutively active germline mutation of the thyrotropin receptor gene as a cause of congenital hyperthyroidism. J Pediatr 1997;131:899-904 https://doi.org/10.1016/S0022-3476(97)70040-4
  9. Holzapfel HP, Wonerow P, von Petrykowski W, Henschen M, Scherbaum WA, Paschke R. Sporadic congenital hyperthyroidism due to a spontaneous germline mutation in the thyrotropin receptor gene. J Clin Endocrinol Metab 1997;82:3879-84 https://doi.org/10.1210/jc.82.11.3879
  10. Kopp P, Jameson JL, Roe TF. Congenital nonautoimmune hyperthyroidism in a nonidentical twin caused by a sporadic germline mutation in the thyrotropin receptor gene. Thyroid 1997;7:765-70 https://doi.org/10.1089/thy.1997.7.765
  11. Alberti L, Proverbio MC, Costagliola S, Weber G, Beck-Peccoz P, Chiumello G, et al. A novel germline mutation in the TSH receptor gene causes non-autoimmune autosomal dominant hyperthyroidism. Eur J Endocrinol 2001;145:249-54 https://doi.org/10.1530/eje.0.1450249
  12. Biebermann H, Schoneberg T, Hess C, Germak J, Gudermann T, Gruters A. The first activating TSH receptor mutation in transmembrane domain 1 identified in a family with nonautoimmune hyperthyroidism. J Clin Endocrinol Metab 2001;86:4429-33 https://doi.org/10.1210/jc.86.9.4429
  13. Kopp P. The TSH receptor and its role in thyroid disease. Cell Mol Life Sci 2001;58:1301-22 https://doi.org/10.1007/PL00000941
  14. Van Sande J, Parma J, Tonacchera M, Swillens S, Dumont J, Vassart G. Somatic and germline mutations of the TSH receptor gene in thyroid diseases. J Clin Endocrinol Metab 1995;80:2577-85 https://doi.org/10.1210/jc.80.9.2577
  15. Corvilain B, Van Sande J, Dumont JE, Vassart G. Somatic and germline mutations of the TSH receptor and thyroid diseases. Clin Endocrinol(Oxf) 2001;55:143-58 https://doi.org/10.1046/j.1365-2265.2001.01365.x
  16. Paschke R, Tonacchera M, Van Sande J, Parma J, Vassart G. Identification and functional characterization of two new somatic mutations causing constitutive activation of the thyrotropin receptor in hyperfunctioning autonomous adenomas of the thyroid. J Clin Endocrinol Metab 1994;79:1785-9 https://doi.org/10.1210/jc.79.6.1785
  17. Parma J, Duprez L, Van Sande J, Hermans J, Rocmans P, Van Vliet G, et al. Diversity and prevalence of somatic mutations in the thyrotropin receptor and Gs alpha genes as a cause of toxic thyroid adenomas. J Clin Endocrinol Metab 1997;82:2695-701 https://doi.org/10.1210/jc.82.8.2695
  18. Parma J, Van Sande J, Swillens S, Tonacchera M, Dumont J, Vassart G. Somatic mutations causing constitutive activity of the thyrotropin receptor are the major cause of hyperfunctioning thyroid adenomas : identification of additional mutations activating both the cyclic adenosine 3',5'-monophosphate and inositol phosphate-Ca2＋ cascades. Mol Endocrinol 1995;9:725-33 https://doi.org/10.1210/me.9.6.725