title: Complete Idiopathic Hypogonadotropic Hypogonadism due to Homozygous GNRH1 Mutations in the Mutational Hot Spots in the Region Encoding the Decapeptide.
abstract: BACKGROUND
  Mutations of the human GNRH1 gene are an extremely rare cause of normosmic idiopathic hypogonadotropic hypogonadism (nIHH), with only 6 mutations so far described.
  
  
  METHODS
  As part of a larger study, families with IHH were screened for mutations in genes known to be associated with IHH. In family 1, a 15-year and 9-month-old boy first presented during infancy with micropenis and bilateral cryptorchidism. His pubic and axillary hair is at stage 4 and 2, respectively. His testes are 1 ml bilaterally, and his stretched penile length is 3.6 cm. In family 2, a 19-year and 2-month-old man was referred because of absence of secondary sexual characteristics. His 13-year and 8-month-old sister did not have any breast development.
  
  
  RESULTS
  In 3 patients from 2 independent families we identified GNRH1 mutations. In the proband from family 1, a homozygous 1-base deletion (c.87delA) leading to a frameshift mutation (p.G29GfsX12) was identified. In family 2, the affected siblings had a novel homozygous mutation of c.G92A leading to p.R31H.
  
  
  CONCLUSIONS
  Both mutations in these families are located in the region encoding the decapeptide and in the loci where the mutations have been described before. Therefore, these areas can be considered as mutational hot spots, indicating priority for routine diagnostic gene mutation analysis.
authors.affiliation: Division of Pediatric Endocrinology, Faculty of Medicine, Cukurova University, Adana, Turkey.
authors.forename: Eda
authors.initials: E
authors.lastname: Mengen
authors.forename: Selma
authors.initials: S
authors.lastname: Tunc
authors.forename: L Damla
authors.initials: LD
authors.lastname: Kotan
authors.forename: Ozlem
authors.initials: O
authors.lastname: Nalbantoglu
authors.forename: Korcan
authors.initials: K
authors.lastname: Demir
authors.forename: Fatih
authors.initials: F
authors.lastname: Gurbuz
authors.forename: Ihsan
authors.initials: I
authors.lastname: Turan
authors.forename: Gül
authors.initials: G
authors.lastname: Seker
authors.forename: Bilgin
authors.initials: B
authors.lastname: Yuksel
authors.forename: A Kemal
authors.initials: AK
authors.lastname: Topaloglu
mesh_terms: D000293:Adolescent; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007006:Hypogonadism / Q000235:genetics*; D008297:Male; D011498:Protein Precursors / Q000235:genetics*; D055815:Young Adult
chemical_list: D011498:Protein Precursors; C050866:progonadoliberin I; D007987:Gonadotropin-Releasing Hormone