Vissers, L.E. et al. Complex chromosome 17p rearrangements associated with low-copy repeats in two patients with congenital anomalies. Hum. Genet. 121, 697-709

Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
Human Genetics (Impact Factor: 4.82). 08/2007; 121(6):697-709. DOI: 10.1007/s00439-007-0359-6
Source: PubMed


Recent molecular cytogenetic data have shown that the constitution of complex chromosome rearrangements (CCRs) may be more complicated than previously thought. The complicated nature of these rearrangements challenges the accurate delineation of the chromosomal breakpoints and mechanisms involved. Here, we report a molecular cytogenetic analysis of two patients with congenital anomalies and unbalanced de novo CCRs involving chromosome 17p using high-resolution array-based comparative genomic hybridization (array CGH) and fluorescent in situ hybridization (FISH). In the first patient, a 4-month-old boy with developmental delay, hypotonia, growth retardation, coronal synostosis, mild hypertelorism, and bilateral club feet, we found a duplication of the Charcot-Marie-Tooth disease type 1A and Smith-Magenis syndrome (SMS) chromosome regions, inverted insertion of the Miller-Dieker lissencephaly syndrome region into the SMS region, and two microdeletions including a terminal deletion of 17p. The latter, together with a duplication of 21q22.3-qter detected by array CGH, are likely the unbalanced product of a translocation t(17;21)(p13.3;q22.3). In the second patient, an 8-year-old girl with mental retardation, short stature, microcephaly and mild dysmorphic features, we identified four submicroscopic interspersed 17p duplications. All 17 breakpoints were examined in detail by FISH analysis. We found that four of the breakpoints mapped within known low-copy repeats (LCRs), including LCR17pA, middle SMS-REP/LCR17pB block, and LCR17pC. Our findings suggest that the LCR burden in proximal 17p may have stimulated the formation of these CCRs and, thus, that genome architectural features such as LCRs may have been instrumental in the generation of these CCRs.

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    • "In addition to this, simple rearrangements account for the vast majority of RAF gene fusions (95%), which is similar to studies of BIR in yeast, where template switching was observed in only 20% of cases (Smith et al. 2007). Unlike other studies that have reported large interspersed duplications and deletions (Lee et al. 2007; Vissers et al. 2007), the complex rearrangements we detected were <2 kb in length and directly adjacent to the breakpoint. Although it is possible that the interspersed copy number changes observed by other groups could occur by "
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