Human Genetics

, Volume 120, Issue 2, pp 227–237

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

  • Zhishuo Ou
  • Małgorzata Jarmuż
  • Steven P. Sparagana
  • Jacques Michaud
  • Jean-Claude Décarie
  • Svetlana A. Yatsenko
  • Beata Nowakowska
  • Patti Furman
  • Chad A. Shaw
  • Lisa G. Shaffer
  • James R. Lupski
  • A. Craig Chinault
  • Sau W. Cheung
  • Paweł Stankiewicz
Original Investigation

DOI: 10.1007/s00439-006-0200-7

Cite this article as:
Ou, Z., Jarmuż, M., Sparagana, S.P. et al. Hum Genet (2006) 120: 227. doi:10.1007/s00439-006-0200-7

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 ∼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 ∼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.

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Zhishuo Ou
    • 1
  • Małgorzata Jarmuż
    • 2
  • Steven P. Sparagana
    • 3
    • 4
  • Jacques Michaud
    • 5
  • Jean-Claude Décarie
    • 5
  • Svetlana A. Yatsenko
    • 1
  • Beata Nowakowska
    • 1
    • 6
  • Patti Furman
    • 1
  • Chad A. Shaw
    • 1
  • Lisa G. Shaffer
    • 2
    • 7
  • James R. Lupski
    • 1
    • 8
    • 9
  • A. Craig Chinault
    • 1
  • Sau W. Cheung
    • 1
  • Paweł Stankiewicz
    • 1
    • 6
  1. 1.Department of Molecular & Human GeneticsBaylor College of MedicineHoustonUSA
  2. 2.Health Research and Education CenterWashington State UniversitySpokaneUSA
  3. 3.Texas Scottish Rite Hospital for ChildrenDallasUSA
  4. 4.Department of NeurologyUniversity of Texas Southwestern Medical SchoolDallasUSA
  5. 5.Research CenterHôpital Sainte-JustineMontrealCanada
  6. 6.Department of Medical GeneticsInstitute of Mother and ChildWarsawPoland
  7. 7.Signature Genomic Laboratories, LLCSpokaneUSA
  8. 8.Department of PediatricsBaylor College of MedicineHoustonUSA
  9. 9.Texas Children’s HospitalHoustonUSA