Mirror-symmetric duplicated chromosome 21q with minor proximal deletion, and with neocentromere in a child without the classical Down syndrome phenotype

We report on a mentally retarded child with multiple minor anomalies and an unusually rearranged chromosome 21, This der(21) chromosome has a deletion of 21p and of proximal 21q whereas the main portion of 21q is duplicated l eading to a mirror-symmetric appearance with the mirror axis at the breakpo int. The centromere is only characterized by a secondary constriction (with a centromeric index of a G; chromosome) at an unexpected distal position, but fluorescence in situ hybridization (FISH) with either chromosome specif ic or with all human centromeres alpha satellite DNA shows no cross hybridi zation. Thus, the marker chromosome represents a further example of an "ana lphoid marker with neocentromere." Molecular analysis using polymorphic mar kers on chromosome 21 verified a very small monosomic segment of the proxim al long arm of chromosome 21, and additionally trisomy of the remaining dis tal segment, Although trisomic for almost the entire 21q arm, our patient s hows no classical Down syndrome phenotype, but only a few minor anomalies f ound in trisomy 21 and in monosomy of proximal 21q, respectively. (C) 2000 Wiley-Liss, Inc.