De novo three-way chromosome translocation 46,XY,t(4;6;21)(p16;p21.1;q21) in a male with cleidocranial dysplasia

Smita M. Purandare, Roberto Mendoza-Londono, Svetlana A. Yatsenko, Dobrawa Napierala, Daryl A. Scott, Tarek Sibai, Kari Casas, Patrick Wilson, Jiyun Lee, Razia Muneer, Joe C. Leonard, Faridali G. Ramji, Ralph Lachman, Shibo Li, Pawel Stankiewicz, Brendan Lee, John J. Mulvihill

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)


Cleidocranial dysplasia (CCD) is an autosomal dominant skeletal dysplasia associated with cranial, clavicular, and dental anomalies. It is caused by mutations in the RUNX2 gene, which encodes an osteoblast-specific transcription factor and maps to chromosome 6p21. We report clinical and molecular cytogenetic studies in a patient with clinical features of CCD including wormian bones, delayed fontanel closure, hypoplastic clavicles and pubic rami, and supernumerary dentition. Additional abnormalities of bone growth and connective tissue, including easy bruisability, scarring, bleeding, joint hypermobility, and developmental delay were also observed. Molecular cytogenetic studies identified a de novo apparently balanced three-way translocation 46,XY,t(4;6;21)(p16;p21.1;q21). Further mapping revealed the breakpoint on 6p21 to be ∼50 kb upstream of exon 1 of the RUNX2 gene, with RUNX2 being intact on the derivative chromosome 6. We hypothesize that the proband's CCD has arisen from disruption of the developmentally regulated gene RUNX2 at the 6p21 breakpoint, due to a position effect mutation which may have altered the expression of the gene. Further studies might unravel a new regulatory element for RUNX2.

Original languageEnglish
Pages (from-to)453-458
Number of pages6
JournalAmerican Journal of Medical Genetics, Part A
Issue number4
Publication statusPublished - 2008 Feb 15
Externally publishedYes


  • Cleidocranial dysplasia (CCD)
  • Fluorescence in situ hybridization (FISH)
  • Phenotype-genotype correlation
  • Three-way chromosome translocation

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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