Physical mapping of nine Xq translocation breakpoints and identification of XPNPEP2 as a premature ovarian failure candidate gene

R. L. Prueitt, J. L. Ross, Andrew R. Zinn

Research output: Contribution to journalArticle

70 Scopus citations


Women with balanced translocations between the long arm of the X chromosome (Xq) and an autosome frequently suffer premature ovarian failure (POF). Two 'critical regions' for POF which extend from Xq13→q22 and from Xq22→q26 have been identified using cytogenetics. To gain insight into the mechanism(s) responsible for ovarian failure in women with X;autosome translocations, we have molecularly characterized the translocation breakpoints of nine X chromosomes. We mapped the breakpoints using somatic cell hybrids retaining the derivative autosome and densely spaced markers from the X-chromosome physical map. One of the POF-associated breakpoints in a critical region (Xq25) mapped to a sequenced PAC clone. The translocation disrupts XPNPEP2, which encodes an Xaa-Pro aminopeptidase that hydrolyzes N- terminal Xaa-Pro bonds. XPNPEP2 mRNA was detected in fibroblasts that carry the translocation, suggesting that this gene at least partially escapes X inactivation. Although the physiologic substrates for the enzyme are not known, XPNPEP2 is a candidate gene for POF. Our breakpoint mapping data will help to identify additional candidate POF genes and to delineate the Xq POF critical region(s). (C) 2000 S. Karger AG, Basel.

Original languageEnglish (US)
Pages (from-to)44-50
Number of pages7
JournalCytogenetics and Cell Genetics
Issue number1-2
StatePublished - Jul 17 2000


ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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