Genetics of human hypogonadotropic hypogonadism

Am J Med Genet. 1999 Dec 29;89(4):240-8. doi: 10.1002/(sici)1096-8628(19991229)89:4<240::aid-ajmg8>3.0.co;2-7.

Abstract

Humans with hypogonadotropic hypogonadism (HH) manifest irreversible pubertal delay, infertility, and low serum levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Although the genetic basis of this condition is largely unknown, mutations have been identified in approximately 5-10% of HH patients. Mutations in the KAL gene (Kallmann syndrome) and the AHC gene (adrenal hypoplasia congenita/HH) cause X-linked recessive HH. Autosomal recessive HH may be brought about by mutations in the gonadotropin-releasing hormone receptor, leptin, and the leptin receptor genes. Isolated deficiencies of the gonadotropins FSH and LH are due to corresponding beta-subunit genes. PROP1 gene mutations lead to combined pituitary deficiency, and HESX gene mutations result in septo-optic dysplasia, both of which include HH. These identified gene mutations advance our understanding of normal hypothalamic-pituitary-gonadal function.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • DAX-1 Orphan Nuclear Receptor
  • DNA-Binding Proteins / genetics
  • Extracellular Matrix Proteins*
  • Female
  • Follicle Stimulating Hormone / blood
  • Follicle Stimulating Hormone / deficiency
  • Follicle Stimulating Hormone / genetics
  • Genes, Homeobox
  • Genes, Recessive
  • Gonadotropins / deficiency*
  • Homeodomain Proteins / genetics
  • Humans
  • Hypogonadism / blood
  • Hypogonadism / diagnosis
  • Hypogonadism / etiology
  • Hypogonadism / genetics*
  • Hypothalamo-Hypophyseal System / metabolism
  • Kallmann Syndrome / genetics
  • Leptin / genetics
  • Luteinizing Hormone / blood
  • Luteinizing Hormone / deficiency
  • Luteinizing Hormone / genetics
  • Male
  • Mutation
  • Nerve Tissue Proteins / genetics
  • Receptors, LHRH / genetics
  • Receptors, Retinoic Acid / genetics
  • Repressor Proteins*
  • Transcription Factors / genetics

Substances

  • ANOS1 protein, human
  • DAX-1 Orphan Nuclear Receptor
  • DNA-Binding Proteins
  • Extracellular Matrix Proteins
  • Gonadotropins
  • Homeodomain Proteins
  • Leptin
  • NR0B1 protein, human
  • Nerve Tissue Proteins
  • Prophet of Pit-1 protein
  • Receptors, LHRH
  • Receptors, Retinoic Acid
  • Repressor Proteins
  • Transcription Factors
  • Luteinizing Hormone
  • Follicle Stimulating Hormone