We thank Dr Ozcelik for his careful reading of our review and his thoughtful letter. Dr Ozcelik raises the issue of nonequivalence of monosomy X frequency and X-chromosome inactivation pattern (XCIP). The first refers to the proportion of cells with a single X chromosome, wherein transcription occurs from the lone X chromosome. The second refers to the ratio of inactivated maternal to paternal X chromosome, wherein transcription does not occur from the inactivated chromosome. We agree that although frequency of monosomy X and XCIP are different, both estimate the degree of inequality in X-chromosome dosage. Thus, while direct comparisons may not be possible, it is reasonable to use them as indices for processes inactivating the X chromosome.
Dr Ozcelik references 2 unpublished studies refuting XCIP skewing in primary biliary cirrhosis. These studies are unavailable to us and we are unable to comment on them.
Finally, our comments about age-related XCIP and the pathogenesis of certain autoimmune diseases have been misinterpreted by Dr Ozcelik. Certainly, many of these autoimmune diseases tend to be more prevalent in older rather than younger patients, and the increased prevalence of XCIP with age suggests there may be some relationship between the two. However, we clearly point out that “no studies have formally linked age related XCIP skewing with the development of autoimmune disease,” and that this topic “deserves further research.”1 Thus, we read with interest Dr Ozcelik's further thoughts on unequal X-chromosome expression and autoimmune disease.
Conflict-of-interest disclosure: The authors declare no competing financial interests.
Correspondence: Josef T. Prchal, University of Utah, School of Medicine, 30 N 1900 E, Room 4C416, Salt Lake City, UT 84112; e-mail:.
- © 2007 by The American Society of Hematology