The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism

Suzy D.C. Bianco, Ursula B. Kaiser

Research output: Contribution to journalReview article

169 Scopus citations

Abstract

Idiopathic hypogonadotropic hypogonadism (IHH) has an incidence of 1-10 cases per 100,000 births. About 60% of patients with IHH present with associated anosmia, also known as Kallmann syndrome, characterized by total or partial loss of olfaction. Many of the gene mutations associated with Kallmann syndrome have been mapped to KAL1 or FGFR1. However, together, these mutations account for only about 15% of Kallmann syndrome cases. More recently, mutations in PROK2 and PROKR2 have been linked to the syndrome and may account for an additional 5-10% of cases. The remaining 40% of patients with IHH have a normal sense of smell. Prior to 2003, the only gene linked to normosmic IHH was the gonadotropinreleasing hormone receptor gene. However, mutations in this receptor are believed to account for only 10% of cases. Subsequently, mutations in KISS1R, TAC3 and TACR3 were identified as causes of normosmic IHH. Certain genes, including PROK2 and FGFR1, are associated with both anosmic and normosmic IHH. Despite recent advances in the field, the genetic causes of the majority of cases of IHH remain unknown. This Review discusses genes associated with hypogonadotropic disorders and the molecular mechanisms by which mutations in these genes may result in IHH.

Original languageEnglish (US)
Pages (from-to)569-576
Number of pages8
JournalNature Reviews Endocrinology
Volume5
Issue number10
DOIs
StatePublished - Oct 1 2009

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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