title: Evidence for involvement of TRE-2 (USP6) oncogene, low-copy repeat and acrocentric heterochromatin in two families with chromosomal translocations.
abstract: 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.
authors.affiliation: Department of Molecular & Human Genetics, Baylor College of Medicine, One Baylor Plaza, Rm T821, Houston, TX 77030, USA.
authors.forename: Zhishuo
authors.initials: Z
authors.lastname: Ou
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Jarmuz
authors.forename: Steven P
authors.initials: SP
authors.lastname: Sparagana
authors.forename: Jacques
authors.initials: J
authors.lastname: Michaud
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Décarie
authors.forename: Svetlana A
authors.initials: SA
authors.lastname: Yatsenko
authors.forename: Beata
authors.initials: B
authors.lastname: Nowakowska
authors.forename: Patti
authors.initials: P
authors.lastname: Furman
authors.forename: Chad A
authors.initials: CA
authors.lastname: Shaw
authors.forename: Lisa G
authors.initials: LG
authors.lastname: Shaffer
authors.forename: James R
authors.initials: JR
authors.lastname: Lupski
authors.forename: A Craig
authors.initials: AC
authors.lastname: Chinault
authors.forename: Sau W
authors.initials: SW
authors.lastname: Cheung
authors.forename: Paweł
authors.initials: P
authors.lastname: Stankiewicz
mesh_terms: D002607:Charcot-Marie-Tooth Disease / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D019457:Chromosome Breakage; D002886:Chromosomes, Human, Pair 17; D010450:Endopeptidases / Q000235:genetics*; D005260:Female; D006570:Heterochromatin / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D015513:Oncogene Proteins / Q000235:genetics*; D011518:Proto-Oncogene Proteins; D012091:Repetitive Sequences, Nucleic Acid; D012689:Sequence Homology, Nucleic Acid; D014178:Translocation, Genetic; D043222:Ubiquitin Thiolesterase
chemical_list: D006570:Heterochromatin; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D010450:Endopeptidases; C473330:USP6 protein, human; D043222:Ubiquitin Thiolesterase