Molecular cytogenetic characterization of two cases with de novo small mosaic supernumerary marker chromosomes derived from chromosome 16: towards a genotype/phenotype correlation

摘要

Small supernumerary marker chromosomes (sSMC) derived from chromosome 16 are rare and, so far, it is not yet clear which regions of chromosome 16 are critical and have clinical consequences. We have characterized two cases with a ring-shaped sSMC derived from chromosome 16. In case A the sSMC was encountered prenatally and was characterized using centromeric fluorescence in situ hybridization (FISH) probes, subcentromere-specific multicolor FISH (subcenM-FISH), reverse FISH and array-CGH, using a full-tiling BAC array specific for chromosome 16. Case B is a postnatal case and the sSMC was characterized by centromeric FISH probes and subcenM-FISH. Our results, using molecular cytogenetics, showed that both sSMC were derived from chromosome 16, resulting in a de novo mosaic partial trisomy of chromosome 16, involving euchromatic material from 16q. Array painting, in case A, allowed the localization of the sSMC breakpoints, revealing that the sSMC comprised the 33.43-47.02 Mb region of chromosome 16 (16p11.2 to 16q12.1), a region known to harbor some protein-coding genes. In general, the phenotypic consequences of a de novo marker chromosome are difficult to assess. Molecular cytogenetics techniques are a valuable tool for the accurate identification of the origin and content of marker chromosomes, contributing to a more informed prenatal counseling and patient follow-up. Besides multicolor FISH approaches, array painting, combining microdissection and array-CGH, is very useful for mapping size and breakpoints of marker chromosomes, since sSMC are often only present in a small percentage of cells.