Molecular cytogenetic studies of children with marker chromosomes

The molecular cytogenetic characterization and clinical description of 15 children with marker chromosomes of unknown nature are presented. By combining both conventional cytogenetic methods (G-, C-, Ag-NOR- and Distamycin-A/DAPI bandings) and molecular techniques (fluorescence in situ hybridization), the chromosomal origin of these markers was successfully determined. The marker chromosomes were first characterized by cytogenetic techniques and later identified by fluorescence in situ hybridization, using a procedure involving stepwise hybridization of chromosome-specific DNA probes (alpha and classical satellites) at various conditions of stringency. There were four cases with bisatellited markers (of chromosome 15 origin), one with acrocentric satellited marker (of chromosome 13 or 21 origin), and two carrying markers that appeared to be autosomal rings (of chromosomes 13 and 18, respectively). The other eight cases belonged to mosaic (n = 5) or nonsupernumerary (n = 3) sex-chromosomal anomalies. Six were of Y and two of X chromosomal origin. Because no familial cases were found, these markers probably developed de novo. In cases of supernumerary marker with satellites, the origin was from acrocentric groups and had common features such as mild to moderate psychomotor retardation and mild facial dysmorphism. In the cases of autosomal ring, multiple anomalies and moderate to severe retardation occurred. For the category of sex-chromosomal origin, stigmata of Turner's syndrome and/or ambiguous genitalia were noted. Mentality was normal.