Evidence for involvement of TRE-2 (USP6) oncogene, low-copy repeat and acrocentric heterochromatin in two families with chromosomal translocations

Department of Molecular & Human Genetics, Baylor College of Medicine, One Baylor Plaza, Rm T821, Houston, TX 77030, USA.
Human Genetics (Impact Factor: 4.82). 10/2006; 120(2):227-37. DOI: 10.1007/s00439-006-0200-7
Source: PubMed


We report clinical findings and molecular cytogenetic analyses for two patients with translocations [t(14;17)(p12;p12) and t(15;17)(p12;p13.2)], in which the chromosome 17 breakpoints map at a large low-copy repeat (LCR) and a breakage-prone TRE-2 (USP6) oncogene, respectively. In family 1, a 6-year-old girl and her 5-year-old brother were diagnosed with mental retardation, short stature, dysmorphic features, and Charcot-Marie-Tooth disease type 1A (CMT1A). G-banding chromosome analysis showed a der(14)t(14;17)(p12;p12) in both siblings, inherited from their father, a carrier of the balanced translocation. Chromosome microarray and FISH analyses revealed that the PMP22 gene was duplicated. The chromosome 17 breakpoint was mapped within an approximately 383 kb LCR17pA that is known to also be the site of several breakpoints of different chromosome aberrations including the evolutionary translocation t(4;19) in Gorilla gorilla. In family two, a patient with developmental delay, subtle dysmorphic features, ventricular enlargement with decreased periventricular white matter, mild findings of bilateral perisylvian polymicrogyria and a very small anterior commissure, a cryptic duplication including the Miller-Dieker syndrome region was identified by chromosome microarray analysis. The chromosome 17 breakpoint was mapped by FISH at the TRE-2 oncogene. Both partner chromosome breakpoints were mapped on the short arm acrocentric heterochromatin within or distal to the rRNA cluster, distal to the region commonly rearranged in Robertsonian translocations. We propose that TRE-2 together with LCR17pA, located approximately 10 Mb apart, also generated the evolutionary gorilla translocation t(4;19). Our results support previous observations that the USP6 oncogene, LCRs, and repetitive DNA sequences play a significant role in the origin of constitutional chromosome aberrations and primate genome evolution.

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    • "In our data, several genes involved in micro-CNAs (9 genes or 10% of all involved genes) mapped to CNAs in close proximity of known break points or hot spots in chromosomes. Those CNAs were either DNA copy number gains (USP6, NAALADL2, BCAS4, DEPDC1B/ELOVL7, BCAS3) (Figure 2C, 3A and 3B) or losses (FAM190A, MACROD2, MTAP) (Figure 2D) [23-31]. Moreover, using the 1 M array CGH platform, we observed several sites of apparent intra-genic alterations in DNA copy number, suggestive of DNA breakage within genes. "
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