X-INACTIVATION PATTERN IN CARRIERS OF X-LINKED RETINITIS-PIGMENTOSA -A VALUABLE MEANS OF PROGNOSTIC EVALUATION

In a large family with X-linked retinitis pigmentosa 2 (XLRP2), we ree xamined 7 obligate carrier females and 6 daughters of obligate carrier s, whose linkage relationships suggested that they carried the XLRP2 g ene. The phenotype varied from totally normal eyes through mild retina l changes to complete loss of vision. The X-inactivation analysis was carried out with the highly informative probe M27beta on DNA from bloo d lymphocytes. This probe detects a locus DXS255 that is differentiall y methylated on the active and inactive X chromosomes. In 5 blind hete rozygotes (aged 43 to 68 years), we found that the X chromosome carryi ng the RP2 gene was methylated and active in nearly all their cells. T he opposite X inactivation pattern was found in a carrier female (aged 45 years) who gave normal findings on eye examination. Carriers with less skewed X inactivation had a less severe clinical outcome. However , we found little or no correlation between their phenotypes and the m ethylation status of their X chromosomes. Our results suggest that it may be possible to develop a predictive test that could identify cases with severe outcome and perhaps cases with normal outcome.