title: Inactivating KISS1 mutation and hypogonadotropic hypogonadism.
abstract: Gonadotropin-releasing hormone (GnRH) is the central regulator of gonadotropins, which stimulate gonadal function. Hypothalamic neurons that produce kisspeptin and neurokinin B stimulate GnRH release. Inactivating mutations in the genes encoding the human kisspeptin receptor (KISS1R, formerly called GPR54), neurokinin B (TAC3), and the neurokinin B receptor (TACR3) result in pubertal failure. However, human kisspeptin loss-of-function mutations have not been described, and contradictory findings have been reported in Kiss1-knockout mice. We describe an inactivating mutation in KISS1 in a large consanguineous family that results in failure of pubertal progression, indicating that functional kisspeptin is important for puberty and reproduction in humans. (Funded by the Scientific and Technological Research Council of Turkey [TÜBİTAK] and others.).
authors.affiliation: Faculty of Medicine, Department of Pediatric Endocrinology, Cukurova University, Adana, Turkey. ktopaloglu@cu.edu.tr
authors.forename: A Kemal
authors.initials: AK
authors.lastname: Topaloglu
authors.forename: Javier A
authors.initials: JA
authors.lastname: Tello
authors.forename: L Damla
authors.initials: LD
authors.lastname: Kotan
authors.forename: Mehmet N
authors.initials: MN
authors.lastname: Ozbek
authors.forename: M Bertan
authors.initials: MB
authors.lastname: Yilmaz
authors.forename: Seref
authors.initials: S
authors.lastname: Erdogan
authors.forename: Fatih
authors.initials: F
authors.lastname: Gurbuz
authors.forename: Fatih
authors.initials: F
authors.lastname: Temiz
authors.forename: Robert P
authors.initials: RP
authors.lastname: Millar
authors.forename: Bilgin
authors.initials: B
authors.lastname: Yuksel
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D003241:Consanguinity; D005260:Female; D005808:Genes, Recessive; D060005:Genotyping Techniques; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D006801:Humans; D007006:Hypogonadism / Q000235:genetics*; D059648:Kisspeptins / Q000235:genetics*; D008297:Male; D009154:Mutation; D010375:Pedigree; D011627:Puberty / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: C106628:KISS1 protein, human; D059648:Kisspeptins; D007987:Gonadotropin-Releasing Hormone