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Familial male-limited precocious puberty (FMPP) is due to constitutive activation of a mutant luteinizing hormone/choriogonadotropin receptor (LH/CGR) leading to elevated testosterone synthesis in testicular Leydig cells. In the present study, we have analyzed the LHCGR gene for members of a Chinese FMPP family.Physical examinations have included assessment of penile length, testicular volume and pubic hair. Bone age assessment, levels of testosterone and gonadotropin-releasing hormone (GnRH) stimulations tests were measured. DNA was extracted from blood samples of the proband and his parents using an QIAGEN Blood DNA Mini Kit. The 11 exons of LHCGR gene were amplified using an AmpliTaq PCR system, and the PCR products were sequenced using an ABI3130xl Genetic Analyzer.The affected boy was 3 year and 1 month old and showed typical clinical manifestation of peripheral precocious puberty. His height was 116.8cm (+5.1s) and Tanner stages were PH 2. Testicular volume was 8 mL bilaterally, penile was 8.5 cm × 2.5 cm. Basal testosterone was 2310 ng/L and bone age was 9 years. GnRH stimulation test revealed a prepubertal response to gonadotropin. The peak of LH was 2.66 IU/L, and the peak of FSH was 1.03 IU/L. Upon sequencing exon 11 of the LHCGR, a heterozygous point mutation of nucleotide 1703 from C to T was detected, which resulted in an amino acid transition from Ala (GCC) to Val (GTC) at position 568. Thus the mutation of LHCGR gene was confirmed to be constitutively active. After treating with aromatase inhibitors for half a year, the patient showed an increase in bone age and height by half a year and 4 cm, respectively. The same point mutation was detected in the patient's father, but did not have any influence on his puberty development.A novel point mutation of the LHCGR gene has been identified in a family affected with FMPP. The c.1703CT mutant LHCGR was confirmed to be constitutively active, which has led to maturation and proliferation of Leydig cells. The variable phenotype within the family suggested variable expressivity of the disease.

To study the causes and prognosis of peripheral precocious puberty.The levels of follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) were detected by a simplified gonadotrophin-releasing hormone (GnRH) stimulation test. The etiologies of 125 children with peripheral precocious puberty were explored by ultrasound scans and bone age assessment. A total of 102 cases were followed up for 3 months to 7.5 years.The etiological distribution of these children was as follows: exogenous hormones intake (n=80), ovarian cyst (n=11), McCune-Albright syndrome (n=11), congenital adrenal hyperplasia (CAH) (n=5), ovarian teratoma (n=1), masculine adrenal tumor (n=1), feminine adrenal tumor (n=1), and handle pituitary tumor (n=1). The causes in 14 cases were unknown. Follow-up showed that the sexual characteristics of 72 cases due to exogenous hormones intake subsided after 1-6 months. Of 11 cases with ovarian cysts, the sexual characteristics subsided spontaneously in 8 cases after 1 to 4 months, but one case was transformed to central precocious puberty after 2 years and three months. One child with ovarian cysts underwent an operation and than the sexual characteristics subsided. The sexual characteristics of the patient who had an ovarian teratoma subsided after operation. The clinical symptoms of children with McCune-Albright syndrome or CAH were alliaviated partly after treatment, and 7 cases were transformed to central precocious puberty. The clinical symptoms of 2 cases of adrenal tumors subsided after operation. One child with handle pituitary tumor died one year after operation.Varied causes may contribute to peripheral precocious puberty and therefore must be carefully identified through history taking, physical examination, and auxiliary examinations. The prognosis may differ for patients with different etiologies of peripheral precocious puberty.