title: NR0B1 Frameshift Mutation in a Boy with Idiopathic Central Precocious Puberty.
abstract: NR0B1 is the causative gene for X-linked adrenal hypoplasia congenita, characterized by adrenal insufficiency, hypogonadotropic hypogonadism, and infertility. We identified an NR0B1 frameshift mutation in a boy with precocious puberty who had no signs of adrenal insufficiency. Blood examination revealed elevated testosterone levels and gonadotropin hyperresponses to gonadotropin releasing hormone (GnRH) stimulation, together with normal adrenal hormone levels. GnRH analog treatment partially ameliorated his clinical features. Molecular analysis identified a p.Glu3fsAla*16 in NR0B1. These results expand the clinical manifestations of NR0B1 mutations to include central precocious puberty without adrenal insufficiency. NR0B1 mutations likely underlie androgen overproduction via GnRH-dependent and -independent mechanisms.
authors.affiliation: Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Hirohito
authors.initials: H
authors.lastname: Shima
authors.forename: Shuichi
authors.initials: S
authors.lastname: Yatsuga
authors.forename: Akie
authors.initials: A
authors.lastname: Nakamura
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Sano
authors.forename: Takako
authors.initials: T
authors.lastname: Sasaki
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Katsumata
authors.forename: Erina
authors.initials: E
authors.lastname: Suzuki
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Hata
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakabayashi
authors.forename: Yukihide
authors.initials: Y
authors.lastname: Momozawa
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kubo
authors.forename: Kohji
authors.initials: K
authors.lastname: Okamura
authors.forename: Shigeo
authors.initials: S
authors.lastname: Kure
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Matsubara
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Ogata
authors.forename: Satoshi
authors.initials: S
authors.lastname: Narumi
authors.forename: Maki
authors.initials: M
authors.lastname: Fukami
mesh_terms: D000728:Androgens / Q000097:blood; D002675:Child, Preschool; D057137:DAX-1 Orphan Nuclear Receptor / Q000235:genetics*; D016368:Frameshift Mutation / Q000235:genetics*; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000627:therapeutic use; D006062:Gonadotropins / Q000097:blood; D006801:Humans; D008297:Male; D011629:Puberty, Precocious / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D013739:Testosterone / Q000097:blood
chemical_list: D000728:Androgens; D057137:DAX-1 Orphan Nuclear Receptor; D006062:Gonadotropins; C539965:NR0B1 protein, human; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone