• Made available online as an Accepted Preprint 28 July 2010
  • Accepted Preprint first posted online on 28 July 2010

Genes involved in human premature ovarian failure

  1. Chiara Cacciatore2,3
  1. 1Dipartimento di Scienze Mediche, Università degli Studi di Milano, Milan I-20100, Italy
    2Laboratorio di Ricerche Endocrinologiche, IRCCS Istituto Auxologico Italiano, Milan I-20100, Italy
    3Unità di Endocrinologia, Fondazione IRCCS Ca' Granda Policlinico, Milan I-20100, Italy
  1. (Correspondence should be addressed to L Persani who is now at Laboratorio di Ricerche Endocrinologiche, Dipartimento di Scienze Mediche, IRCCS Istituto Auxologico Italiano, Università di Milano, Via Zucchi 18, 20095 Cusano, Milan, Italy; Email: luca.persani{at}unimi.it)


Premature ovarian failure (POF) is an ovarian defect characterized by the premature depletion of ovarian follicles before the age of 40 years, representing one major cause of female infertility. POF relevance is continuously growing because women tend to conceive ever more frequently in their thirties and forties. POF can present very early with a pubertal defect. More frequently, it is the end stage of an occult process (primary ovarian insufficiency, POI) affecting ∼1–2% of under-40 women. POI is a heterogeneous disease caused by a variety of mechanisms. Though the underlying cause remains unexplained in the majority of cases, various data indicate that POI has a strong genetic component. These data include the existence of several causal genetic defects in humans, experimental and natural models, as well as the frequent familiarity. The variable expressivity of POI defect in women of the same family may indicate that, in addition to some monogenic forms, POI may frequently be considered as a multifactorial defect resulting from the contribution of several predisposing alleles. The X chromosome-linked defects play a major role among the presently known causal defects. Here, we review the principal X-linked and autosomal genes involved in syndromic and nonsyndromic forms of POI with the wish that this list will soon become upgraded because of the discovery of novel contributing mechanisms. A better understanding of POI pathogenesis will indeed allow the construction of tests able to predict the age of menopause in women at higher risk of POI.

  • Revision received 2 July 2010
  • Accepted 28 July 2010
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