Two generations of 13-15 chromosomal mosaicism: possible evidence for a genetic defect in the control of chromosomal replication

Abstract

An identical nontranslocation autosomal mosaicism occurring in two consecutive generations is presented. A mother and two of her four daughters have been demonstrated to be 46/47 mosaics. The trisomic cells have an extra autosome in the 13–15, or D, group. The proband and one of her sisters reveal varying phenotypic expressions of the trisomic state. The mother and her two other daughters are phenotypically normal. The observation of 46/47 chromosomal mosaicism in man in a pattern which suggests that it is under genetic control necessitates the introduction of a new theory since it cannot be explained by earlier hypotheses which are directed towards understanding the chance occurrence of an individual mosaic. The rapidly accumulating evidence of the nonrandomness of chromosomal abnormalities points towards a possible defect in primary gene control of DNA replication. It is theorized that a gene which regulates the replication of a chromosome in the 13–15, or D, group is defective and that, as a result, this chromosome replicates twice instead of once during some, but not all mitoses, producing a mosaic of trisomic and normal cells. Presumably, the postulated mutant gene is present in the heterozygous state in the affected individuals and behaves as a dominant, with half of the children of an affected parent being abnormal.