[The genetic basis of premature ovarian failure]

Premature ovarian failure is defined by the association of amenorrhea, elevated levels of serum gonadotropins and hypoestrogenism occuring before the age of forty. In a growing number of these cases, genetic disorders have been shown to be involved. Cytogenetic abnormalities predominantly concern the X chromosome, including Turner syndrome, but also rearrangements such as deletions and X-autosome translocations. Molecular investigation of these abnormalities has led to the identification of a number of candidate genes most of them still having unknown functions. Testing for premutation of the FMR1 gene, whose full mutation determines the fragile X syndrome, is particularly worthwhile in these patients because of its high frequency, not only among the patients with ovarian failure but also in the general population. Other, much less frequent mutations have been located for example in the gonadotropin and gonadotropin receptor genes and their study contributes to the understanding of ovarian physiology. Here we review most of the etiologies which have to be taken in account in the genetic screening of premature ovarian failure patients.