How to cite this article: Cottrell CE, Sommer A, Wenger GD, Bullard S, Busch T, Krahn KN, Lidral AC, Gastier-Foster JM. 2009. Atypical X-chromosome inactivation in an X;1 translocation patient demonstrating Xq28 functional disomy. Am J Med Genet Part A 149A:408–414.
Atypical X-chromosome inactivation in an X;1 translocation patient demonstrating Xq28 functional disomy†
Article first published online: 12 FEB 2009
Copyright © 2009 Wiley-Liss, Inc.
American Journal of Medical Genetics Part A
Volume 149A, Issue 3, pages 408–414, March 2009
How to Cite
Cottrell, C. E., Sommer, A., Wenger, G. D., Bullard, S., Busch, T., Krahn, K. N., Lidral, A. C. and Gastier-Foster, J. M. (2009), Atypical X-chromosome inactivation in an X;1 translocation patient demonstrating Xq28 functional disomy. Am. J. Med. Genet., 149A: 408–414. doi: 10.1002/ajmg.a.32699
- Issue published online: 24 FEB 2009
- Article first published online: 12 FEB 2009
- Manuscript Accepted: 26 NOV 2008
- Manuscript Received: 10 MAR 2008
- NIH. Grant Numbers: R01 DE014677, KO2DE015291
- March of Dimes. Grant Number: 6-FY01-616
- X-chromosome inactivation;
- X;1 translocation;
- Xq28 functional disomy;
X-chromosome inactivation (XCI) is an epigenetic process used to regulate gene dosage in mammalian females by silencing genes on one X-chromosome. While the pattern of XCI is typically random in normal females, abnormalities of the X-chromosome may result in skewing due to disadvantaged cell growth. We describe a female patient with an X;1 translocation [46,X,t(X;1)(q28;q21)] and unusual pattern of XCI who demonstrates functional disomy of the Xq28 region distal to the translocation breakpoint. There was complete skewing of XCI in the patient, along with the atypical findings of an active normal X chromosome and an inactive derivative X. Characterization of the translocation revealed that the patient's Xq28 breakpoint interrupts the DKC1 gene. Molecular analysis of the breakpoint region revealed functional disomy of Xq28 genes distal to DKC1. We propose that atypical XCI occurred in the patient due to a post-inactivation cell selection mechanism likely initiated by disruption of DKC1. As a result, the pattern of XCI is opposite that of the expected for an X;autosome translocation. Therefore, we suggest the phenotypic abnormalities found in the patient are a result of functional disomy in the Xq28 region. © 2009 Wiley-Liss, Inc.