GnRH receptor gene mutations in adolescents and young adults presenting with signs of partial gonadotropin deficiency

Show full item record



Permalink

http://hdl.handle.net/10138/229916

Citation

Hietamaki , J , Hero , M , Holopainen , E , Kansakoski , J , Vaaralahti , K , Iivonen , A-P , Miettinen , P J & Raivio , T 2017 , ' GnRH receptor gene mutations in adolescents and young adults presenting with signs of partial gonadotropin deficiency ' , PLoS One , vol. 12 , no. 11 , 0188750 . https://doi.org/10.1371/journal.pone.0188750

Title: GnRH receptor gene mutations in adolescents and young adults presenting with signs of partial gonadotropin deficiency
Author: Hietamaki, Johanna; Hero, Matti; Holopainen, Elina; Kansakoski, Johanna; Vaaralahti, Kirsi; Iivonen, Anna-Pauliina; Miettinen, Paivi J.; Raivio, Taneli
Contributor organization: Raivio Group
Children's Hospital
Department of Physiology
Department of Obstetrics and Gynecology
HUS Gynecology and Obstetrics
Research Programs Unit
Research Programme for Molecular Neurology
Timo Pyry Juhani Otonkoski / Principal Investigator
HUS Children and Adolescents
Date: 2017-11-28
Language: eng
Number of pages: 11
Belongs to series: PLoS One
ISSN: 1932-6203
DOI: https://doi.org/10.1371/journal.pone.0188750
URI: http://hdl.handle.net/10138/229916
Abstract: Biallelic, partial loss-of-function mutations in GNRHR cause a wide spectrum of reproductive phenotypes from constitutional delay of growth and puberty to complete congenital hypogonadotropic hypogonadism. We studied the frequency of GNRHR, FGFR1, TAC3, and TACR3 mutations in nine adolescent and young adult females with clinical cues consistent with partial gonadotropin deficiency (stalled puberty, unexplained secondary amenorrhea), and describe phenotypic features and molecular genetic findings of monozygotic twin brothers with stalled puberty. Two girls out of nine (22%, 95% CI 6-55%) carried biallelic mutations in GNRHR. The girl with compound heterozygous c. 317A>G p.(Gln106Arg) and c. 924_926delCTT p.(Phe309del) GNRHR mutations displayed incomplete puberty and clinical signs of hypoestrogenism. The patient carrying a homozygous c. 785G> A p.(Arg262Gln) mutation presented with signs of hypoestrogenism and unexplained secondary amenorrhea. None of the patients exhibited mutations in FGFR1, TAC3, or TACR3. The twin brothers, compound heterozygous for GNRHR mutations c. 317A> G p.(Gln106Arg) and c. 785G>A p.(Arg262Gln), presented with stalled puberty and were discordant for weight, and the heavier of them had lower testosterone levels. These results suggest that genetic testing of the GNRHR gene should be offered to adolescent females with low-normal gonadotropins and unexplained stalled puberty or menstrual dysfunction. In male patients with partial gonadotropin deficiency, excess adipose tissue may suppress hypothalamic-pituitary-gonadal axis.
Subject: IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM
FUNCTIONAL HYPOTHALAMIC AMENORRHEA
HOMOZYGOUS R262Q MUTATION
HORMONE RECEPTOR
DELAYED PUBERTY
CONSTITUTIONAL DELAY
DIAGNOSIS
REVERSAL
GROWTH
TESTOSTERONE
3111 Biomedicine
3123 Gynaecology and paediatrics
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


Files in this item

Total number of downloads: Loading...

Files Size Format View
file.pdf 3.178Mb PDF View/Open

This item appears in the following Collection(s)

Show full item record