Low grade mosaicism in marker chromosomes

Small supernumerary marker chromosomes (sSMC) are structurally abnormal chromosomes that cannot be thoroughly characterized by conventional banding cytogenetics and are equal in size or smaller than a chromosome 20. They are present in 0.075%of prenatal cases, and overall ~3 million people worldwide are carriers of an sSMC. First described already in 1961 it is known now that in ~70% of the de novo cases sSMC have no phenotypic effects. Nonetheless, in at least 30– 50% of the prenatally detected sSMC cases the pregnancy is terminated. I.e. in a certain percentage of potentially healthy children with sSMC an abortion is induced. This situation can only be improved by providing more and more reliable information on sSMC (e.g. http://www.med.uni-jena.de/fish/sSMC/00START. htm). One typical feature of sSMC carriers is that they are frequently mosaics: more than 70% of the reported cases have a normal cell line besides the one with the additional sSMC. The cell line with an sSMC is in one tenth of the cases present in only up to 30% of the studied tissue cells. Recently, also a tendency towards cryptic mosaicism in sSMC cases was reported. Cryptic mosaicism means, that karyotypic evolution of an sSMC can happen during lifetime of its carrier. These changes can e.g. lead to a mosaic like: 47, XX, +min(9)(:p12>q12:) /47, XX, +min(9)(:p12->q12::q12->p12:)/47, XX, +r(9) (::p12->q12::)/47, XX, +r(9)(::p12->q12::p12->q12::)x2/46, XX. Even more than generally valid for mosaic, it is true in sSMC cases, that mosaicism is expressed differently in different cell types of an sSMC carrier. This was recently exemplarily proven in an induced aborted case with an sSMC(1): in all 13 studied different body tissues of the fetus the percentage of cells with an sSMC varied. The range was from 13% in amnion cells to 62% in heart muscle cells. This observation showed that there is no possibility to find a representative mosaic state for an individual by studying one, two or three tissues. This might be an explanation why it was by not possible to correlate the mosaic-state of sSMC carriers with the clinical outcome. E.g. it is known that partial tri-or tetrasomy 15q13.1 is normally associated with severe clinical symptoms. However, there are already five such mosaic sSMC cases reported with normal phenotypes. Overall, mosaiscm is one major problem inmarker chromosome diagnostics. It has to be stressed, that it is a problem only faceable by single cell directed (molecular) cytogenetic and not multi cell based array-/ chip-approaches.