title: [Analysis of a family affected with familial male-limited precocious puberty due to a Ala568Val mutation in LHCGR gene].
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  A novel point mutation of the LHCGR gene has been identified in a family affected with FMPP. The c.1703C>T 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.
authors.affiliation: Department of Endocrinology, Fuzhou Children's Hospital, Fujian Medical University Teaching Hospital, Fuzhou, Fujian 350005, P R China. chenrm321@sina.com.cn
authors.forename: Rui-min
authors.initials: RM
authors.lastname: Chen
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiao-hong
authors.initials: XH
authors.lastname: Yang
authors.forename: Xiang-quan
authors.initials: XQ
authors.lastname: Lin
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D001483:Base Sequence; D002675:Child, Preschool; D003062:Codon; D005091:Exons; D006801:Humans; D008297:Male; D008958:Models, Molecular; D009154:Mutation; D011487:Protein Conformation; D011629:Puberty, Precocious / Q000175:diagnosis / Q000235:genetics*; D011974:Receptors, LH / Q000737:chemistry / Q000235:genetics*
chemical_list: D003062:Codon; D011974:Receptors, LH