title: Distribution of gene mutations associated with familial normosmic idiopathic hypogonadotropic hypogonadism.
abstract: OBJECTIVE
  Normosmic idiopathic hypogonadotropic hypogonadism (nIHH) is characterized by failure of initiation or maintenance of puberty due to insufficient gonadotropin release, which is not associated with anosmia/hyposmia. The objective of this study was to determine the distribution of causative mutations in a hereditary form of nIHH.
  
  
  METHODS
  In this prospective collaborative study, 22 families with more than one affected individual (i.e. multiplex families) with nIHH were recruited and screened for genes known or suspected to be strong candidates for nIHH.
  
  
  RESULTS
  Mutations were identified in five genes (GNRHR, TACR3, TAC3, KISS1R, and KISS1) in 77% of families with autosomal recessively inherited nIHH. GNRHR and TACR3 mutations were the most common two causative mutations occurring with about equal frequency.
  
  
  CONCLUSIONS
  Mutations in these five genes account for about three quarters of the causative mutations in nIHH families with more than one affected individual. This frequency is significantly greater than the previously reported rates in all inclusive (familial plus sporadic) cohorts. GNRHR and TACR3 should be the first two genes to be screened for diagnostic purposes. Identification of causative mutations in the remaining families will shed light on the regulation of puberty.
authors: Çukurova University Faculty of Medicine, Department of Pediatric Endocrinology, Balcalı, Adana, Turkey.
authors: Fatih
authors: F
authors: Gürbüz
authors: L Damla
authors: LD
authors: Kotan
authors: Eda
authors: E
authors: Mengen
authors: Zeynep
authors: Z
authors: Şıklar
authors: Merih
authors: M
authors: Berberoğlu
authors: Sebila
authors: S
authors: Dökmetaş
authors: Mehmet Fatih
authors: MF
authors: Kılıçlı
authors: Ayla
authors: A
authors: Güven
authors: Birgül
authors: B
authors: Kirel
authors: Nurçin
authors: N
authors: Saka
authors: Şükran
authors: Ş
authors: Poyrazoğlu
authors: Yaşar
authors: Y
authors: Cesur
authors: Murat
authors: M
authors: Doğan
authors: Samim
authors: S
authors: Özen
authors: Mehmet Nuri
authors: MN
authors: Özbek
authors: Hüseyin
authors: H
authors: Demirbilek
authors: M Burcu
authors: MB
authors: Kekil
authors: Fatih
authors: F
authors: Temiz
authors: Neslihan
authors: N
authors: Önenli Mungan
authors: Bilgin
authors: B
authors: Yüksel
authors: Ali Kemal
authors: AK
authors: Topaloğlu
mesh_terms: D000293:Adolescent; D000328:Adult; D015331:Cohort Studies; D005192:Family Health; D056726:Genetic Association Studies; D006801:Humans; D007006:Hypogonadism / Q000151:congenital / Q000235:genetics* / Q000378:metabolism; D007223:Infant; D059648:Kisspeptins / Q000235:genetics / Q000378:metabolism; D008297:Male; D009154:Mutation; D015287:Neurokinin B / Q000235:genetics / Q000378:metabolism; D011446:Prospective Studies; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D000074502:Receptors, Kisspeptin-1; D011966:Receptors, LHRH / Q000235:genetics* / Q000378:metabolism; D018042:Receptors, Neurokinin-3 / Q000235:genetics* / Q000378:metabolism; D015320:Tachykinins / Q000235:genetics / Q000378:metabolism; D014421:Turkey; D055815:Young Adult
chemical_list: C484844:GNRHR protein, human; C106628:KISS1 protein, human; C118688:KISS1R protein, human; D059648:Kisspeptins; D020033:Protein Isoforms; D043562:Receptors, G-Protein-Coupled; D000074502:Receptors, Kisspeptin-1; D011966:Receptors, LHRH; D018042:Receptors, Neurokinin-3; D015320:Tachykinins; D015287:Neurokinin B