Characterization of a de novo complex chromosome rearrangement (CCR) involving chromosomes 2 and 12,, associated with mental retardation and impaired speech development

We report on a currently six-year-old patient with a de novo complex chromosome rearrangement (CCR) involving chromosomes 2 and 12. A translocation 2; 12 that appeared to be reciprocal after standard banding turned out to be a complex event with seven breaks after molecular cytogenetic analyses. Array CGH analysis showed no imbalances at the breakpoints but revealed an additional microdeletion of about 80 kb on chromosome 11. The same deletion was also present in the phenotypically normal father. The patient showed relatively mild mental retardation, defined mainly as impaired speech development (orofacial dyspraxia) and psychomotor retardation. In addition, mild dysmorphic facial features like hypertelorism, a prominent philtrum and down-turned corners of the mouth were observed. We narrowed down all breakpoint regions to about 100 kb, using a panel of mapped bacterial artificial chromosome (BAC) clones for fluorescence in situ hybridization (FISH). BACs spanning or flanking all seven breakpoints were identified and no chromosomal imbalances were found consistent with the array CGH results. Our investigations resulted in the following karyotype: 46,XY,t(2;12)(2pter -> 2p25.3::2p23.3 -> 2p25.2 -> 2p23.3 -> 2p14::2q4.3-2p14 -> 2q14.3 -> 2q14.3::12q 12 -> 12qter;12pter -> 12q12::2p25.3 -> 2p25.2::2q14.3 -> 2qter).