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Familial Male-Limited Precocious Puberty

  • Nerissa C. Kreher
Part of the Contemporary Endocrinology book series (COE)

Abstract

Familial male-limited precocious puberty (FMPP), also known as testotoxicosis, is a rare, dominantly inherited disorder that causes gonadotropin-independent sexual precocity in boys. Early signs of puberty, including virilization, growth acceleration, and skeletal advancement, develop in affected boys, usually by 3 years of age. Activating mutations of the human luteinizing hormone (LH) receptor result in increased testosterone production by the Leydig cells despite low LH levels. Diagnosis, molecular analysis, and therapy for FMPP are discussed.

Key words

Testotoxicosis LH receptor mutation Gonadotropin-independent precocious puberty Biclutamide 

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References

  1. 1.
    Rosenthal SM, Grumbach MM, Kaplan SL. Gonadotropin-independent familial sexual precocity with premature Leydig and germinal cell maturation (familial testotoxicosis): effects of a potent luteinizing hormone-releasing factor agonist and medroxyprogesterone acetate therapy in four cases. J Clin Endocrinol Metab 1983;57:571–579.PubMedCrossRefGoogle Scholar
  2. 2.
    Egli CA, Rosenthal SM, Grumbach MM, Montalvo JM, Gondos B. Pituitary gonadotropinindependent male-limited autosomal dominant sexual precocity in nine generations: familial testotoxicosis. J Pediatr 1985;106:33–40.PubMedCrossRefGoogle Scholar
  3. 3.
    Wu SM, Leschek EW, Rennert OM, Chan WY. Luteinizing hormone receptor mutations in disorders of sexual development and cancer. Front Biosci 2000;5:D343–D352.PubMedCrossRefGoogle Scholar
  4. 4.
    Rosenthal IM, Refetoff S, Rich B et al. Response to challenge with gonadotropin-releasing hormone agonist in a mother and her two sons with a constitutively activating mutation of the luteinizing hormone receptor–a clinical research center study. J Clin Endocrinol Metab 1996;81:3802–3806.PubMedCrossRefGoogle Scholar
  5. 5.
    Leschek E. Familial male-limited precocious puberty. The Endocrinologist 2004;14:148–151.CrossRefGoogle Scholar
  6. 6.
    Lim YJ, Low LC. Familial testotoxicosis in a Chinese family. Eur J Pediatr 1994;153:241–4.PubMedCrossRefGoogle Scholar
  7. 7.
    Holland F. Gonadotropin-independent precocious puberty. Endocrinol Metab Clin North Am 1991;20:191–210.PubMedGoogle Scholar
  8. 8.
    Beas F, Zurbrugg RP, Leibow SG, Patton RG, Gardner LI. Familial male sexual precocity: report of the the eleventh kindred found, with observations on blood group linkage and urinary C19-steroid excretion. J Clin Endocrinol Metab 1962;22:1095–1102.PubMedCrossRefGoogle Scholar
  9. 9.
    Mortimer E. Family constitutional precocious puberty in a boy three years of age. Pediatrics 1954;13:174–177.PubMedGoogle Scholar
  10. 10.
    Jungck EC, Brown NH, Carmona N. Constitutional precocious puberty in the male. Am J Dis Child 1956;91:138–143.Google Scholar
  11. 11.
    Wierman ME, Beardsworth DE, Mansfield MJ et al. Puberty without gonadotropins. A unique mechanism of sexual development. N Engl J Med 1985;312:65–72.PubMedCrossRefGoogle Scholar
  12. 12.
    Frost GJ, Parkin JM, Scott D, Watson MJ. Pseudo-precocious puberty caused by bilateral idiopathic testicular hyperplasia. Acta Paediatr Scand 1985;74:623–628.PubMedCrossRefGoogle Scholar
  13. 13.
    Gondos B, Egli CA, Rosenthal SM, Grumbach MM. Testicular changes in gonadotropin-independent familial male sexual precocity. Familial testotoxicosis. Arch Pathol Lab Med 1985;109:990–995.Google Scholar
  14. 14.
    Schedewie HK, Reiter EO, Beitins IZ et al. Testicular Leydig cell hyperplasia as a cause of familial sexual precocity. J Clin Endocrinol Metab 1981;52:271–278.PubMedCrossRefGoogle Scholar
  15. 15.
    Apter D. Ultrasensitive new immunoassays for gonadotropins in the evaluation of puberty. Curr Opin Pediatr 1993;5:481–487.PubMedGoogle Scholar
  16. 16.
    Steinberger E, Root A, Ficher M, Smith KD. The role of androgens in the initiation of spermatogenesis in man. J Clin Endocrinol Metab 1973;37:746–751.PubMedCrossRefGoogle Scholar
  17. 17.
    Lee P. Pediatric Endocrinology, 4th edition. New York: Marcel-Dekker, 2003.Google Scholar
  18. 18.
    Ibanez L, Potau N, Zampolli M et al. Use of leuprolide acetate response patterns in the early diagnosis of pubertal disorders: comparison with the gonadotropin-releasing hormone test. J Clin Endocrinol Metab 1994;78:30–35.PubMedCrossRefGoogle Scholar
  19. 19.
    Styne D. Pediatric Endocrinology, 2nd edition. Philadelphia, PA: WB Saunders, 2002.Google Scholar
  20. 20.
    Liu G, Duranteau L, Carel JC, Monroe J, Doyle DA, Shenker A. Leydig-cell tumors caused by an activating mutation of the gene encoding the luteinizing hormone receptor. N Engl J Med 1999;341:1731–1736.PubMedCrossRefGoogle Scholar
  21. 21.
    Edeburn GF, Mortensson W. Value of bone scan in the McCune-Albright syndrome. Report of a case. Acta Radiol 1986;27:719–721.Google Scholar
  22. 22.
    Manasco PK, Girton ME, Diggs RL et al. A novel testis-stimulating factor in familial male precocious puberty. N Engl J Med 1991;324:227–231.PubMedCrossRefGoogle Scholar
  23. 23.
    Kremer H, Mariman E, Otten BJ et al. Cosegregation of missense mutations of the luteinizing hormone receptor gene with familial male-limited precocious puberty. Hum Mol Genet 1993;2:1779–1783.PubMedCrossRefGoogle Scholar
  24. 24.
    Shenker A, Laue L, Kosugi S, Merendino JJ Jr, Minegishi T, Cutler GB Jr. A constitutively activating mutation of the luteinizing hormone receptor in familial male precocious puberty. Nature 1993;365:652–654.PubMedCrossRefGoogle Scholar
  25. 25.
    Minegishi T, Nakamura K, Takakura Y et al. Cloning and sequencing of human LH/hCG receptor cDNA. Biochem Biophys Res Commun 1990;172:1049–1054.PubMedCrossRefGoogle Scholar
  26. 26.
    Hong S, Ryu KS, Oh MS, Ji I, Ji TH. Roles of transmembrane prolines and proline-induced kinks of the lutropin/choriogonadotropin receptor. J Biol Chem 1997;272:4166–4171.PubMedCrossRefGoogle Scholar
  27. 27.
    Rodriguez MC, Segaloff DL. The orientation of the lutropin/choriogonadotropin receptor in rat luteal cells as revealed by site-specific antibodies. Endocrinology 1990;127:674–681.PubMedCrossRefGoogle Scholar
  28. 28.
    Ascoli M, Segaloff DL. The lutropin/choriogonadotropin receptor, a 2002 perspective. Endocr Rev 2002;23:141–174.PubMedCrossRefGoogle Scholar
  29. 29.
    Rousseau-Merck MF, Misrahi M, Atger M, Loosfelt H, Milgrom E, Berger R. Localization of the human luteinizing hormone/choriogonadotropin receptor gene (LHCGR) to chromosome 2p21. Cytogenet Cell Genet 1990;54:77–79.PubMedCrossRefGoogle Scholar
  30. 30.
    Huhtaniemi I. The Parkes lecture. Mutations of gonadotrophin and gonadotrophin receptor genes:what do they teach us about reproductive physiology? J Reprod Fertil 2000;119:173–186.PubMedCrossRefGoogle Scholar
  31. 31.
    Latronico AC, Shinozaki H, Guerra G Jr et al. Gonadotropin-independent precocious puberty due to luteinizing hormone receptor mutations in Brazilian boys: a novel constitutively activating mutation in the first transmembrane helix. J Clin Endocrinol Metab 2000;85:4799–4805.PubMedCrossRefGoogle Scholar
  32. 32.
    Hirakawa T, Ascoli M. A constitutively active somatic mutation of the human lutropin receptor found in Leydig cell tumors activates the same families of G proteins as germ line mutations associated with Leydig cell hyperplasia. Endocrinology 2003;144:3872–3878.PubMedCrossRefGoogle Scholar
  33. 33.
    Richter-Unruh A, Wessels HT, Menken U et al. Male LH-independent sexual precocity in a 3.5-year-old boy caused by a somatic activating mutation of the LH receptor in a Leydig cell tumor. J Clin Endocrinol Metab 2002;87:1052–1056.PubMedCrossRefGoogle Scholar
  34. 34.
    Themmen APN, Huhtaniemi IT. Mutations of gonadotropins and gonadotropin receptors: elucidating the physiology and pathophysiology of pituitary-gonadal function. Endocr Rev 2000;21: 551–583.PubMedCrossRefGoogle Scholar
  35. 35.
    Laue L, Wu SM, Kudo M et al. Heterogeneity of activating mutations of the human luteinizing hormone receptor in male-limited precocious puberty. Biochem Mol Med 1996;58:192–198.PubMedCrossRefGoogle Scholar
  36. 36.
    Laue L, Chan WY, Hsueh AJ et al. Genetic heterogeneity of constitutively activating mutations of the human luteinizing hormone receptor in familial male-limited precocious puberty. Proc Natl Acad Sci USA 1995;92:1906–1910.PubMedCrossRefGoogle Scholar
  37. 37.
    Kremer H, Marten JW, van Reen M et al. A limited repertoire of mutations of the luteinizing hormone (LH) receptor gene in familial and sporadic patients with male LH-independent precocious puberty. J Clin Endocrinol Metab 1999;84:1136–1140.PubMedCrossRefGoogle Scholar
  38. 38.
    Latronico AC, Anasti J, Arnhold IJP et al. A novel mutation of the luteinizing hormone receptor gene causing male gonadotropin-independent precocious puberty. J Clin Endocrinol Metab 1995;80:2490–2494.PubMedCrossRefGoogle Scholar
  39. 39.
    Latronico AC, Billerbeck AE, Pinto EM, Brazile D’Alva C, Arnhold IJ, Mendonca BB. Maternal isodisomy causing homozygosity for a dominant activating mutation of the luteinizing hormone receptor gene in a boy with familial male-limited precocious puberty. Clin Endocrinol 2003;59:533–534.CrossRefGoogle Scholar
  40. 40.
    Kosugi S, Mori T, Shenker A. The role of Asp578 in maintaining the inactive conformation of the human lutropin/choriogonadotropin receptor. J Biol Chem 1996;271:31813–31817.PubMedCrossRefGoogle Scholar
  41. 41.
    Babovic-Vuksanovic D, Donaldson MD, Gibson NA, Wallace AM. Hazards of ketoconazole therapy in testotoxicosis. Acta Paediatr 1994;83:994–997.PubMedCrossRefGoogle Scholar
  42. 42.
    Muller J, Gondos B, Kosugi S, Mori T, Shenker A. Severe testotoxicosis phenotype associated with Asp578?Tyr mutation of the lutrophin/choriogonadotrophin receptor gene. J Med Genet 1998;35:340–341.PubMedCrossRefGoogle Scholar
  43. 43.
    Clark PA, Clarke WL. Testotoxicosis. An unusual presentation and novel gene mutation. Clin Pediatr 1995;34:271–274.CrossRefGoogle Scholar
  44. 44.
    Evans BA, Bowen DJ, Smith PJ, Clayton PE, Gregory JW. A new point mutation in the luteinizing hormone receptor gene in familial and sporadic male limited precocious puberty: genotype does not always correlate with phenotype. J Med Genet 1996;33:143–147.PubMedCrossRefGoogle Scholar
  45. 45.
    Kreher NC, Pescovitz OH. Potent New Therapy for Familial Male-Limited Precocious Puberty. Endocrine Society and San Diego, CA, 2005:139–140.Google Scholar
  46. 46.
    Iiri T, Herzmark P, Nakamoto JM, van Dop C, Bourne HR. Rapid GDP release from Gs alpha in patients with gain and loss of endocrine function. Nature 1994;371:164–168.PubMedCrossRefGoogle Scholar
  47. 47.
    Nakamoto JM, Zimmerman D, Jones EA et al. Concurrent hormone resistance (pseudohypoparathyroidism type Ia) and hormone independence (testotoxicosis) caused by a unique mutation in the G alpha s gene. Biochem Mol Med 1996;58:18–24.PubMedCrossRefGoogle Scholar
  48. 48.
    Herrlich A, Kuhn B, Grosse R, Schmid A, Schultz G, Gudermann T. Involvement of Gs and Gi proteins in dual coupling of the luteinizing hormone receptor to adenylyl cyclase and phospholipase C. J Biol Chem 1996;271:16764–16772.PubMedCrossRefGoogle Scholar
  49. 49.
    Gudermann T, Kalkbrenner F, Schulz G. Diversity and selectivity of receptor-G protein interaction. Annu Rev Pharmacol Toxicol 1996;36:429–459.PubMedCrossRefGoogle Scholar
  50. 50.
    Kosugi S, Mori T, Shenker A. An anionic residue at position 564 is important for maintaining the inactive conformation of the human lutropin/choriogonadotropin receptor. Mol Pharmacol 1998;53:894–901.PubMedGoogle Scholar
  51. 51.
    Zhang M, Mizrachi D, Fanelli F, Segaloff DL. The formation of a salt bridge between helices 3 and 6 is responsible for the constitutive activity and lack of hormone responsiveness of the naturally occurring L457R mutation of the human lutropin receptor. J Biol Chem 2005;280:26169–26176.PubMedCrossRefGoogle Scholar
  52. 52.
    Bertelloni S, Baroncelli GI, Lala R et al. Long-term outcome of male-limited gonadotropinindependent precocious puberty. Horm Res 1997;48:235–239.PubMedCrossRefGoogle Scholar
  53. 53.
    Holland FJ, Fishman L, Bailey JD, Fazekas AT. Ketoconazole in the management of precocious puberty not responsive to LHRH-analogue therapy. N Engl J Med 1985;312:1023–1028.PubMedCrossRefGoogle Scholar
  54. 54.
    Barbieri RL, Ryan KJ. Direct effects of medroxyprogesterone acetate (MPA) and megestrol acetate (MGA) on rat testicular steroidogenesis. Acta Endocrinol 1980;94:419–425.PubMedGoogle Scholar
  55. 55.
    Satyaswaroop PG, Gurpide E. A direct effect of medroxyprogesterone acetate on 17 etahydroxysteroid dehydrogenase in adult rat testis. Endocrinology 1978;102:1761–1765.PubMedCrossRefGoogle Scholar
  56. 56.
    Rosenthal SM, Grumbach MM, Kaplan SL. Gonadotropin-independent familial sexual precocity with premature Leydig and germinal cell maturation (familial testotoxicosis): effects of a potent luteinizing hormone-releasing factor agonist and medroxyprogesterone acetate therapy in four cases.J Clin Endocrinol Metab 1983;57:571–579.PubMedCrossRefGoogle Scholar
  57. 57.
    Itoh K, Nakada T, Kubota Y, Suzuki H, Ishigooka M, Izumi T. Testotoxicosis proved by immunohistochemical analysis and successfully treated with cyproterone acetate. Urol Int 1996;57:199–202.PubMedCrossRefGoogle Scholar
  58. 58.
    Pont A, Williams PL, Azhar S et al. Ketoconazole blocks testosterone synthesis. Arch Intern Med 1982;142:2137–2140.PubMedCrossRefGoogle Scholar
  59. 59.
    Santen RJ, Van den Bossche H, Symoens J, Brugmans J, DeCoster R. Site of action of low dose ketoconazole on androgen biosynthesis in men. J Clin Endocrinol Metab 1983;57:732–736.PubMedCrossRefGoogle Scholar
  60. 60.
    Holland FJ, Kirsch SE, Selby R. Gonadotropin-independent precocious puberty (“testotoxicosis”): influence of maturational status on response to ketoconazole. J Clin Endocrinol Metab 1987;64:328–333.PubMedCrossRefGoogle Scholar
  61. 61.
    Soriano-Guillen L, Lahlou N, Chauvet G, Roger M, Chaussain JL, Carel JC. Adult height after ketoconazole treatment in patients with familial male-limited precocious puberty. J Clin Endocrinol Metab 2005;90:147–151.PubMedCrossRefGoogle Scholar
  62. 62.
    Robertson MH, Rich P, Parker F, Hanifin JM. Ketoconazole in griseofulvin-resistant dermatophytosis. J Am Acad Dermatol 1982;6:224–229.PubMedCrossRefGoogle Scholar
  63. 63.
    UpToDate. Ketoconazole: Drug Information, 13.3 edition. LexiComp Online™, 2006.Google Scholar
  64. 64.
    Bernuau J, Durand F, Pessayre D. Ketoconazole-induced hepatotoxicity. Hepatology 1997;26:802.PubMedCrossRefGoogle Scholar
  65. 65.
    Lake-Bakaar G, Scheuer PJ, Sherlock S. Hepatic reactions associated with ketoconazole in the United Kingdom. Br Med J (Clin Res Ed) 1987;294:419–422.CrossRefGoogle Scholar
  66. 66.
    Cutler GB Jr, Cassorla FG, Ross JL et al. Pubertal growth: physiology and pathophysiology. Recent Prog Horm Res 1986;42:443–470.PubMedGoogle Scholar
  67. 67.
    Morishima A, Grumbach MM, Simpson ER, Fisher C, Qin K. Aromatase deficiency in male and female siblings caused by a novel mutation and the physiological role of estrogens. J Clin Endocrinol Metab 1995;80:3689–3698.PubMedCrossRefGoogle Scholar
  68. 68.
    Smith EP, Boyd J, Frank GR et al. Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man. N Engl J Med 1994;331:1056–1061.PubMedCrossRefGoogle Scholar
  69. 69.
    Ismail AA, Barth JH. Endocrinology of gynaecomastia. Ann Clin Biochem 2001;38:596–607.PubMedCrossRefGoogle Scholar
  70. 70.
    Leschek EW, Jones J, Barnes KM, Hill SC, Cutler GB Jr. Six-year results of spironolactone and testolactone treatment of familial male-limited precocious puberty with addition of deslorelin after central puberty onset. J Clin Endocrinol Metab 1999;84:175–178.PubMedCrossRefGoogle Scholar
  71. 71.
    Leschek EW, Jones J, Chan WY. Effect of Spironolactone, Testolactone, and Deslorelin Treatment on the Final Height of Boys With Familial Male-Limited Precocious Puberty (FMPP). LWPES/ESPE 6th Joint Meeting, Abstract P2-854, Montreal, 2001.Google Scholar
  72. 72.
    UpToDate. Testolactone: Drug Information, 13.3 edition. LexiComp onlineTM 2006.Google Scholar
  73. 73.
    Bennet CL, Raisch DW, Sartor O. Pneumonitis associated with nonsteroidal antiandrogens: presumptive evidence of a class effect. Ann Intern Med 2002;137:625.Google Scholar
  74. 74.
    Brueggemeier RW, Hackett JC, Diaz-Cruz ES. Aromatase inhibitors in the treatment of breast cancer. Endocr Rev 2005;26:331–345.PubMedCrossRefGoogle Scholar
  75. 75.
    Roth C, Freiberg C, Zappel H, Albers N. Effective aromatase inhibition by anastrozole in a patient with gonadotropin-independent precocious puberty in McCune-Albright syndrome. J Pediatr Endocrinol 2002;15(Suppl 3):945–948.Google Scholar
  76. 76.
    Riepe FG, Baus I, Wiest S, Krone N, Sippell WG, Partsch CJ. Treatment of pubertal gynecomastia with the specific aromatase inhibitor anastrozole. Horm Res 2004;62:113–118.PubMedCrossRefGoogle Scholar
  77. 77.
    Mauras N, O’Brien KO, Klein KO, Hayes V. Estrogen suppression in males: metabolic effects. J Clin Endocrinol Metab 2000;85:2370–2377.PubMedCrossRefGoogle Scholar
  78. 78.
    Mauras N, Welch S, Rini A, Klein KO. An open label 12-month pilot trial on the effects of the aromatase inhibitor anastrozole in growth hormone (GH)-treated GH deficient adolescent boys. J Pediatr Endocrinol 2004;17:1597–1606.CrossRefGoogle Scholar
  79. 79.
    Kreher NC, Pescovitz OH, Delameter P, Tiulpakov A, Hochberg Z. Treatment of familial malelimited precocious puberty with bicalutamide and anastrozole. J Pediatr 2006;149:416–420.PubMedCrossRefGoogle Scholar
  80. 80.
    Kreher NC, Pescovitz OH, Delameter P, Tiulpakov A, Hochberg Z. Extended Follow-up of the Use of Bicalutamide and Anastrozole in FMPP. Boston, MA: Endocrine Society, 2006.Google Scholar
  81. 81.
    Reiter EO, Brown RS, Longcope C, Beitins IZ. Male-limited familial precocious puberty in three generations. Apparent Leydig-cell autonomy and elevated glycoprotein hormone alpha subunit. N Engl J Med 1984;311:515–519.PubMedCrossRefGoogle Scholar
  82. 82.
    Leschek EW, Chan WY, Diamond DA et al. Nodular Leydig cell hyperplasia in a boy with familial male-limited precocious puberty. J Pediatr 2001;138:949–951.PubMedCrossRefGoogle Scholar
  83. 83.
    Martin MM, Wu SM, Martin AL, Rennert OM, Chan WY. Testicular seminoma in a patient with a constitutively activating mutation of the luteinizing hormone/chorionic gonadotropin receptor. Eur J Pediatr 1998;139:101–106.Google Scholar
  84. 84.
    Rajpert-De Meyts E, Skakkabaek NE. The possible role of sex hormones in the development of testicular cancer. Eur Urol 1993;23:54–59, discussion 60–61.Google Scholar
  85. 85.
    Richter-Unruh A, Wessels HT, Menken U et al. Male LH-independent sexual precocity in a 3.5-year-old boy caused by a somatic activating mutation of the LH receptor in a Leydig cell tumor. J Clin Endocrinol Metab 2002;87:1052–1056.PubMedCrossRefGoogle Scholar
  86. 86.
    Gromoll J, Partsch CJ, Simoni M et al. A mutation in the first transmembrane domain of the lutropin receptor causes male precocious puberty. J Clin Endocrinol Metab 1998;83:476–480.PubMedCrossRefGoogle Scholar
  87. 87.
    Kraaij R, Post M, Kremer H et al. A missense mutation in the second transmembrane segment of the luteinizing hormone receptor causes familial male-limited precocious puberty. J Clin Endocrinol Metab 1995;80:3168–3172.PubMedCrossRefGoogle Scholar
  88. 88.
    Yano K, Kohn LD, Saji M, Kataoka N, Okuno A, Cutler GB Jr. A case of male-limited precocious puberty caused by a point mutation in the second transmembrane domain of the luteinizing hormone choriogonadotropin receptor gene. Biochem Biophys Res Commun 1996;220:1036–1042.PubMedCrossRefGoogle Scholar
  89. 89.
    Latronico AC, Abell AN, Arnhold IJ et al. A unique constitutively activating mutation in third transmembrane helix of luteinizing hormone receptor causes sporadic male gonadotropin-independent precocious puberty. J Clin Endocrinol Metab 1998;83:2435–2440.PubMedCrossRefGoogle Scholar
  90. 90.
    Kosugi S, Van Dop C, Geffner ME et al. Characterization of heterogeneous mutations causing constitutive activation of the luteinizing hormone receptor in familial male precocious puberty. Hum Mol Genet 1995;4:183–188.PubMedCrossRefGoogle Scholar
  91. 91.
    Yano K, Saji M, Hidaka A et al. A new constitutively activating point mutation in the luteinizing hormone/choriogonadotropin receptor gene in cases of male-limited precocious puberty. J Clin Endocrinol Metab 1995;80:1162–1168.PubMedCrossRefGoogle Scholar
  92. 92.
    Kawate N, Kletter GB, Wilson BE, Netzloff ML, Menon KM. Identification of constitutively activating mutation of the luteinising hormone receptor in a family with male limited gonadotrophin independent precocious puberty (testotoxicosis). J Med Genet 1995;32:553–554.PubMedCrossRefGoogle Scholar
  93. 93.
    Cocco S, Meloni A, Marini MG, Cao A, Moi P. A missense (T577I) mutation in the luteinizing hormone receptor gene associated with familial male-limited precocious puberty. Hum Mutat 1996;7:164–166.PubMedCrossRefGoogle Scholar
  94. 94.
    Yano K, Hidaka A, Saji M et al. A sporadic case of male-limited precocious puberty has the same constitutively activating point mutation in luteinizing hormone/choriogonadotropin receptor gene as familial cases. J Clin Endocrinol Metab 1994;79:1818–1823.PubMedCrossRefGoogle Scholar
  95. 95.
    Wu SM, Leschek EW, Brain C, Chan WY. A novel luteinizing hormone receptor mutation in a patient with familial male-limited precocious puberty: effect of the size of a critical amino acid on receptor activity. Mol Genet Metab 1999;66:68–73.PubMedCrossRefGoogle Scholar

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© Humana Press Inc. 2007

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  • Nerissa C. Kreher

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