title: Molecular analysis of the neuropeptide Y1 receptor gene in human idiopathic gonadotropin-dependent precocious puberty and isolated hypogonadotropic hypogonadism.
abstract: OBJECTIVE
  To investigate the role of mutations or polymorphisms in the NPY-Y1R gene in human idiopathic central pubertal disorders.
  
  
  METHODS
  Molecular studies.
  
  
  METHODS
  University hospital.
  
  
  METHODS
  Thirty-three patients with gonadotropin-dependent precocious puberty, 22 with hypogonadotropic hypogonadism, and 50 controls.
  
  
  METHODS
  Genomic DNA extraction, NPY-Y1R gene sequence analysis, cell-surface expression, and functional activity of an identified receptor variant.
  
  
  METHODS
  Results of sequencing, cell-surface receptor expression, and receptor function.
  
  
  RESULTS
  A heterozygous substitution of lysine (K) by threonine (T) at position 374 in the carboxyl terminal region of NPY-Y1R was identified in a girl with familial GDPP. Her mother, who had pubertal developmental at appropriate age, carried the same genetic variant. Introduction of the K374T variant into an expression vector containing the human NPY-Y1R complementary DNA led to a partial reduction in cell-surface expression of NPY-Y1R in transiently transfected HEK293 cells. This mutation did not lead to a significant reduction in NPY-stimulated activity of the receptor in this heterologous expression system. No other allelic variants of the NPY-Y1R gene were identified in patients or controls.
  
  
  CONCLUSIONS
  We have identified an inherited heterozygous variant of the NPY-Y1R gene in a girl with precocious puberty; however, this most likely did not contribute to her phenotype. Mutations of the highly conserved NPY-Y1R gene do not appear to represent a frequent mechanism underlying human idiopathic central pubertal disorders.
authors.affiliation: Developmental Endocrinology Unit, Hormone and Molecular Genetics Laboratory, Clinical Hospital, São Paulo University Medical School, São Paulo, Brazil. karinamf@brturbo.com.br <karinamf@brturbo.com.br>
authors.forename: Karina Cocco Monteiro
authors.initials: KC
authors.lastname: Freitas
authors.forename: Ginny
authors.initials: G
authors.lastname: Ryan
authors.forename: Vinicius Nahime
authors.initials: VN
authors.lastname: Brito
authors.forename: Ya-Xiong
authors.initials: YX
authors.lastname: Tao
authors.forename: Elaine Maria Frade
authors.initials: EM
authors.lastname: Costa
authors.forename: Berenice Bilharinho
authors.initials: BB
authors.lastname: Mendonca
authors.forename: Deborah
authors.initials: D
authors.lastname: Segaloff
authors.forename: Ana Claudia
authors.initials: AC
authors.lastname: Latronico
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007006:Hypogonadism / Q000235:genetics*; D007223:Infant; D008297:Male; D017354:Point Mutation; D011629:Puberty, Precocious / Q000235:genetics*; D017476:Receptors, Neuropeptide Y / Q000235:genetics*
chemical_list: D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor