A mitotically stable marker chromosome negative for whole chromosome libraries, centromere probes and chromosome specific telomere regions: a novel class of supernumerary marker chromosome?

A two year-old child presented with mild developmental delay. On karyotype analysis, a supernumerary small marker chromosome (SMC) was found in all ce lls examined. This SMC was approximately the size of an isochromosome 18p, being symmetrical with a central constriction, C-banding and silver stainin g were negative and FISH with all chromosome-specific paints, centromere pr obes and telomere probes showed no hybridization to the SMC; telomere repea t sequences were however present on both arms. Comparative genomic hybridiz ation showed no amplification of any chromosome region. Flow sorting of the SMC and reverse painting onto normal metaphase spreads showed no hybridiza tion to any chromosome, whereas reverse painting onto the patient's own met aphases showed hybridization to the SMC only. This SMC may thus represent e ither a complex amplicon of different genomic regions, or a multifold ampli fication of a very small region, with a neocentromere comprising an active kinetochore but no alphoid DNA. Prognostic implications for the proband wer e difficult to assess due to the absence of reports of similar marker chrom osomes in the literature. Copyright (C) 2001 S. Karger AG, Basel.