How to Cite this Article: van Binsbergen E, Hochstenbach R, Giltay J, Swinkels M. 2012. Unstable transmission of a familial complex chromosome rearrangement. Am J Med Genet Part A 158A: 2888–2893.
Unstable transmission of a familial complex chromosome rearrangement†
Article first published online: 17 SEP 2012
Copyright © 2012 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A
Special Issue: SPECIAL ISSUE: GROWTH CHARTS IN GENETIC SYNDROMES
Volume 158A, Issue 11, pages 2888–2893, November 2012
How to Cite
van Binsbergen, E., Hochstenbach, R., Giltay, J. and Swinkels, M. (2012), Unstable transmission of a familial complex chromosome rearrangement. Am. J. Med. Genet., 158A: 2888–2893. doi: 10.1002/ajmg.a.35580
- Issue published online: 17 OCT 2012
- Article first published online: 17 SEP 2012
- Manuscript Accepted: 25 JUN 2012
- Manuscript Received: 14 MAR 2012
- complex chromosome rearrangement;
- inverted duplication with a terminal deletion;
- unstable transmission;
Complex chromosome rearrangements (CCRs) are rare genomic structural aberrations involving three or more breakpoints on two or more chromosomes. About one-third of all CCRs are familial. Transmittance of such a CCR results either in genomic imbalance due to abnormal segregation at meiosis I or is stably passed on to the next generation. Here we present a phenotypically normal mother with a CCR involving chromosomes 1, 3, and 5 that gave birth to a phenotypically abnormal son. The boy presented with hypotonia, mild facial dysmorphisms, and severe intellectual disability. Conventional karyotyping revealed the same apparently balanced CCR as in the mother. However, by use of array-comparative genome hybridization (array-CGH) and fluorescence in situ hybridization (FISH) we discovered that one of the derivative chromosomes in the patient contained a de novo rearrangement. It appears that during transmission of the CCR, an additional de novo deletion and duplication had arisen in one of the derivative chromosomes. We speculate that this was the result of the inverted duplication with a distal deletion mechanism. We also demonstrate the importance of high-resolution breakpoint analysis in CCRs and stress that genetic counseling of a familial CCR is not straightforward. To our knowledge, this would be the first description of this mechanism operating on a structurally abnormal chromosome. © 2012 Wiley Periodicals, Inc.