title: Mutational analysis of TAC3 and TACR3 genes in patients with idiopathic central pubertal disorders.
abstract: OBJECTIVE
  To investigate the presence of variants in the TAC3 and TACR3 genes, which encode NKB and its receptor (NK3R), respectively, in a large cohort of patients with idiopathic central pubertal disorders.
  
  
  METHODS
  Two hundred and thirty seven patients were studied: 114 with central precocious puberty (CPP), 73 with normosmic isolated hypogonadotropic hypogonadism (IHH), and 50 with constitutional delay of growth and puberty (CDGP). The control group consisted of 150 Brazilian individuals with normal pubertal development. Genomic DNA was extracted from peripheral blood and the entire coding region of both TAC3 and TACR3 genes were amplified and automatically sequenced.
  
  
  RESULTS
  We identified one variant (p.A63P) in NKB and four variants, p.G18D, p.L58L (c.172C>T), p.W275* and p.A449S in NK3R, which were absent in the control group. The p.A63P variant was identified in a girl with CPP, and p.A449S in a girl with CDGP. The known p.G18D, p.L58L, and p.W275* variants were identified in three unrelated males with normosmic IHH.
  
  
  CONCLUSIONS
  Rare variants in the TAC3 and TACR3 genes were identified in patients with central pubertal disorders. Loss-of-function variants of TACR3 were associated with the normosmic IHH phenotype.
authors: Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil.
authors: Cintia
authors: C
authors: Tusset
authors: Sekoni D
authors: SD
authors: Noel
authors: Ericka B
authors: EB
authors: Trarbach
authors: Letícia F G
authors: LF
authors: Silveira
authors: Alexander A L
authors: AA
authors: Jorge
authors: Vinicius N
authors: VN
authors: Brito
authors: Priscila
authors: P
authors: Cukier
authors: Stephanie B
authors: SB
authors: Seminara
authors: Berenice B de
authors: BB
authors: Mendonça
authors: Ursula B
authors: UB
authors: Kaiser
authors: Ana Claudia
authors: AC
authors: Latronico
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006130:Growth Disorders / Q000235:genetics*; D006801:Humans; D007006:Hypogonadism / Q000235:genetics*; D008297:Male; D015287:Neurokinin B / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011628:Puberty, Delayed / Q000235:genetics*; D011629:Puberty, Precocious / Q000235:genetics*; D018042:Receptors, Neurokinin-3 / Q000235:genetics*; D055815:Young Adult
chemical_list: D018042:Receptors, Neurokinin-3; D015287:Neurokinin B