A novel mosaic complex supernumerary marker chromosome in a girl with seizures: systematic characterization of the complex marker

Abstract Small supernumerary marker chromosomes(sSMC) are a heterogeneous group of chromosomeswhich are reported in variable phenotypes. They are chromosomalfragments or markers whose origins often cannot be determined by conventional cytogenetic methods alone and require molecular approaches. In general sSMC are equal in size or smaller than chromosome 20. The complex sSMC (CsSMC) arise from two different chromosomes. The aim of the present study is to identify and characterize the chromosomalabnormality in an 11 year old girl with seizures, intellectual disability and developmental delay. Different methods like GTG banding, C-banding and NOR staining, spectral karyotyping (SKY), fluorescence in-situ hybridization (FISH) using whole chromosome paintprobes (WCP) and bacterial artificial chromosome(BAC) clones were used. Also array CGH was done to check the gains and losses in the genome. The chromosomal analysison the metaphases revealed a karyotype of mos 47,XX,+mar/46,XX. The marker was identified by SKY and aCGH, as a 33 Mb duplication of the 3q region and a 38 Mb duplication of the chromosome9p region. This was confirmed by WCP FISH. Further fine mapping was done with 8 BAC clones from the 3q and 9p regions to confirm the marker chromosome. The marker showed the centromeric 9 region which was also confirmed by the BAC clones. The application of the combined cytogenetic methods like aCGH and FISH helped in the systematic characterization of the CsSMC. The accurate characterization of the CsSMC helps in increasing the knowledge of chromosomalorigin, gene content, UPD and other imbalance in the genome.