Human Reproduction, Vol 12, 2641-2648, Copyright © 1997 by Oxford University Press
S Franks, N Gharani, D Waterworth, S Batty, D White, R Williamson and M McCarthy
Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women
of reproductive age. Familial clustering of cases suggests that genetic
factors play an important part in its aetiology. A number of studies of
families with several cases of PCOS have produced results suggesting an
autosomal dominant trait. Detailed analysis of a large number of affected
families has, however, cast some doubt about the mode of inheritance. An
autosomal dominant trait remains possible but a more complex aetiology
seems more likely. The results of our recent studies support the concept of
an oligogenic disorder in which genes affecting metabolic pathways in
glucose homeostasis and steroid biosynthesis are both involved. We review
evidence for an important role for the insulin gene minisatellite in the
aetiology of anovulatory PCOS and for the gene coding for P450 cholesterol
side chain cleavage (CYP11a) in the mechanism of excessive androgen
secretion in women with polycystic ovaries. We propose that the
heterogeneity of clinical and biochemical features in PCOS can be explained
by the interaction of a small number of key genes with environmental,
particularly nutritional, factors.
REVIEWS
The genetic basis of polycystic ovary syndrome
Department of Obstetrics and Gynaecology, Imperial College School of Medicine, St Mary's Hospital, London, UK.
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|
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|
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|
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