Genotype and phenotype of patients with gonadotropin-releasing hormone receptor mutations

Hyung Goo Kim, Jennifer Pedersen-White, Balasubramanian Bhagavath, Lawrence C. Layman

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Human mutations in the gonadotropin-releasing hormone receptor (GNRHR) gene cause autosomal recessive, normosmic idiopathic hypogonadotropic hypogonadism (IHH). At least 19 different mutations have been identified in this G-protein-coupled receptor, which consist mostly of missense mutations. The Gln106Arg and Arg262Gln mutations comprise nearly half of the identified alleles. Most mutations impair ligand binding and all compromise cell signaling events. Some of the mutations also adversely affect activation of gonadotropin subunit or Gnrhr gene promoters. Interestingly, a number of the mutant GnRHRs can be rescued in vitro from misfolding and degradation within the cell by the addition of a GnRHR antagonist IN3. Most affected patients have compound heterozygous GNRHR mutations that may cause either complete IHH (no evidence of puberty) or incomplete IHH (partial evidence of puberty), although some genotypes are associated with mild disease in some families and severe disease in others. GNRHR mutations also appear to cause constitutional delay of puberty, and one genotype (homozygosity for Gln106Arg) may be reversible in patients with IHH. Mutations in the human GNRHR gene have contributed greatly to the understanding of normosmic IHH, as well as the structure and function of the GnRHR.

Original languageEnglish (US)
Pages (from-to)94-110
Number of pages17
JournalFrontiers of Hormone Research
Volume39
DOIs
StatePublished - Apr 8 2010

Fingerprint

LHRH Receptors
Genes
Genotype
Phenotype
Mutation
Cell signaling
Puberty
G-Protein-Coupled Receptors
Gonadotropins
Chemical activation
Ligands
Degradation
Missense Mutation
Alleles
Idiopathic Hypogonadotropic Hypogonadism

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Genotype and phenotype of patients with gonadotropin-releasing hormone receptor mutations. / Kim, Hyung Goo; Pedersen-White, Jennifer; Bhagavath, Balasubramanian; Layman, Lawrence C.

In: Frontiers of Hormone Research, Vol. 39, 08.04.2010, p. 94-110.

Research output: Contribution to journalArticle

Kim, Hyung Goo ; Pedersen-White, Jennifer ; Bhagavath, Balasubramanian ; Layman, Lawrence C. / Genotype and phenotype of patients with gonadotropin-releasing hormone receptor mutations. In: Frontiers of Hormone Research. 2010 ; Vol. 39. pp. 94-110.
@article{ff18117413d84611874b7998b86db428,
title = "Genotype and phenotype of patients with gonadotropin-releasing hormone receptor mutations",
abstract = "Human mutations in the gonadotropin-releasing hormone receptor (GNRHR) gene cause autosomal recessive, normosmic idiopathic hypogonadotropic hypogonadism (IHH). At least 19 different mutations have been identified in this G-protein-coupled receptor, which consist mostly of missense mutations. The Gln106Arg and Arg262Gln mutations comprise nearly half of the identified alleles. Most mutations impair ligand binding and all compromise cell signaling events. Some of the mutations also adversely affect activation of gonadotropin subunit or Gnrhr gene promoters. Interestingly, a number of the mutant GnRHRs can be rescued in vitro from misfolding and degradation within the cell by the addition of a GnRHR antagonist IN3. Most affected patients have compound heterozygous GNRHR mutations that may cause either complete IHH (no evidence of puberty) or incomplete IHH (partial evidence of puberty), although some genotypes are associated with mild disease in some families and severe disease in others. GNRHR mutations also appear to cause constitutional delay of puberty, and one genotype (homozygosity for Gln106Arg) may be reversible in patients with IHH. Mutations in the human GNRHR gene have contributed greatly to the understanding of normosmic IHH, as well as the structure and function of the GnRHR.",
author = "Kim, {Hyung Goo} and Jennifer Pedersen-White and Balasubramanian Bhagavath and Layman, {Lawrence C.}",
year = "2010",
month = "4",
day = "8",
doi = "10.1159/000312696",
language = "English (US)",
volume = "39",
pages = "94--110",
journal = "Frontiers of Hormone Research",
issn = "0301-3073",
publisher = "S. Karger AG",

}

TY - JOUR

T1 - Genotype and phenotype of patients with gonadotropin-releasing hormone receptor mutations

AU - Kim, Hyung Goo

AU - Pedersen-White, Jennifer

AU - Bhagavath, Balasubramanian

AU - Layman, Lawrence C.

PY - 2010/4/8

Y1 - 2010/4/8

N2 - Human mutations in the gonadotropin-releasing hormone receptor (GNRHR) gene cause autosomal recessive, normosmic idiopathic hypogonadotropic hypogonadism (IHH). At least 19 different mutations have been identified in this G-protein-coupled receptor, which consist mostly of missense mutations. The Gln106Arg and Arg262Gln mutations comprise nearly half of the identified alleles. Most mutations impair ligand binding and all compromise cell signaling events. Some of the mutations also adversely affect activation of gonadotropin subunit or Gnrhr gene promoters. Interestingly, a number of the mutant GnRHRs can be rescued in vitro from misfolding and degradation within the cell by the addition of a GnRHR antagonist IN3. Most affected patients have compound heterozygous GNRHR mutations that may cause either complete IHH (no evidence of puberty) or incomplete IHH (partial evidence of puberty), although some genotypes are associated with mild disease in some families and severe disease in others. GNRHR mutations also appear to cause constitutional delay of puberty, and one genotype (homozygosity for Gln106Arg) may be reversible in patients with IHH. Mutations in the human GNRHR gene have contributed greatly to the understanding of normosmic IHH, as well as the structure and function of the GnRHR.

AB - Human mutations in the gonadotropin-releasing hormone receptor (GNRHR) gene cause autosomal recessive, normosmic idiopathic hypogonadotropic hypogonadism (IHH). At least 19 different mutations have been identified in this G-protein-coupled receptor, which consist mostly of missense mutations. The Gln106Arg and Arg262Gln mutations comprise nearly half of the identified alleles. Most mutations impair ligand binding and all compromise cell signaling events. Some of the mutations also adversely affect activation of gonadotropin subunit or Gnrhr gene promoters. Interestingly, a number of the mutant GnRHRs can be rescued in vitro from misfolding and degradation within the cell by the addition of a GnRHR antagonist IN3. Most affected patients have compound heterozygous GNRHR mutations that may cause either complete IHH (no evidence of puberty) or incomplete IHH (partial evidence of puberty), although some genotypes are associated with mild disease in some families and severe disease in others. GNRHR mutations also appear to cause constitutional delay of puberty, and one genotype (homozygosity for Gln106Arg) may be reversible in patients with IHH. Mutations in the human GNRHR gene have contributed greatly to the understanding of normosmic IHH, as well as the structure and function of the GnRHR.

UR - http://www.scopus.com/inward/record.url?scp=77956214752&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77956214752&partnerID=8YFLogxK

U2 - 10.1159/000312696

DO - 10.1159/000312696

M3 - Article

C2 - 20389088

AN - SCOPUS:84925955981

VL - 39

SP - 94

EP - 110

JO - Frontiers of Hormone Research

JF - Frontiers of Hormone Research

SN - 0301-3073

ER -