Abstract The aim of the study was to provide a descriptive analysis of familial male-limited precocious puberty (FMPP), which is a rare inherited disease caused by heterozygous constitutively activating mutations of the luteinizing hormone/choriogonadotropin receptor gene (LHCGR). The patient was a ten-month-old boy, presenting with penile enlargement, pubic hair formation, and spontaneous erections. Based on the clinical manifestations and laboratory data, including sexual characteristics, serum testosterone levels, GnRH stimulation test, and bone age, this boy was diagnosed with peripheral precocious puberty. Subsequently the precocious puberty-related genes were analyzed by direct DNA sequencing of amplified PCR products from the patient and his parents. Genetic analysis revealed a novel heterozygous missense mutation c.1732G > C (Asp578His) of the LHCGR gene exon11 in the patient, which had never been reported. His parents had no mutations. After combined treatment with aromatase inhibitor letrozole and anti-androgen spironolactone for six months, the patient's symptoms were controlled. The findings in this study expand the mutation spectrum of the LHCGR gene, and provide molecular evidence for the etiologic diagnosis as well as for the genetic counseling and prenatal diagnosis in the family.
WANG Min,LI Min,LIU Yue-Sheng et al. Familial male-limited precocious puberty due to Asp578His mutations in the LHCGR gene:clinical characteristics and gene analysis in an infant[J]. CJCP, 2017, 19(11): 1159-1164.
WANG Min,LI Min,LIU Yue-Sheng et al. Familial male-limited precocious puberty due to Asp578His mutations in the LHCGR gene:clinical characteristics and gene analysis in an infant[J]. CJCP, 2017, 19(11): 1159-1164.
Schedewie HK, Reiter EO, Beitins IZ, et al. Testicular leydig cell hyperplasia as a cause of familial sexual precocity[J]. J Clin Endocrinol Metab, 1981, 52(2):271-278.
[2]
Shenker A, Laue L, Kosugi S, et al. A constitutively activating mutation of the luteinizing hormone receptor in familial male precocious puberty[J]. Nature, 1993, 365(6447):652-654.
[3]
Kremer H, Mariman E, Otten BJ, et al. Cosegregation of missense mutations of the luteinizing hormone receptor gene with familial male-limited precocious puberty[J]. Hum Mol Genet, 1993, 2(11):1779-1783.
[4]
Themmen AP. An update of the pathophysiology of human gonadotrophin subunit and receptor gene mutations and polymorphisms[J]. Reproduction, 2005, 130(3):263-274.
[5]
Nagasaki K, Katsumata N, Ogawa Y, et al. Novel C617Y mutation in the 7th transmembrane segment of luteinizing hormone/choriogonadotropin receptor in a Japanese boy with peripheral precocious puberty[J]. Endocr J, 2010, 57(12):1055-1060.
[6]
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[J]. Proc Natl Acad Sci U S A, 1995, 92(6):1906-1910.
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]. J Clin Endocrinol Metab, 1994, 79(6):1818-1823.
[11]
Nagasaki K, Katsumata N, Ogawa Y, et al. Novel C617Y mutation in the 7th transmembrane segment of luteinizing hormone/choriogonadotropin receptor in a Japanese boy with peripheral precocious puberty[J]. Endocr J, 2010, 57(12):1055-1060.
[12]
Martin MM, Wu SM, Martin AL, et al. Testicular seminoma in a patient with a constitutively activating mutation of the luteinizing hormone/chorionic gonadotropin receptor[J]. Eur J Endocrinol, 1998, 139(1):101-106.
