X chromosome abnormalities are the leading identifiable cause of premature ovarian failure (POF). POF-related abnormalities range from the complete absence of one X- chromosome to assorted deletions and translocations to mutations in specific genes. The diversity of X chromosome abnormalities associated with POF indicates that the disorder is genetically heterogeneous. Potential molecular mechanisms include both dominant and receive mutations in X-linked genes as well as nonspecific chromosome effects that impair meiosis. A list of candidate X-linked POF genes is emerging from molecular studies of X chromosome abnormalities, data from the Human Genome Project and related functional genomics projects, and the results of gene targeting experiments in mice. Mutational analysis of candidate genes in a large number of women with idiopathic POF is needed to determine which of these genes contribute to the cause of this disorder.
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