FISH characterization of two supernumerary r(1) associated with distinct clinical phenotypes

Only a few reports on supernumerary r(1) chromosomes associated with a clin ical phenotype have been published. We describe two unrelated patients with congenital malformations and developmental delay who were found to have a de novo supernumerary r(1) in 50% (Case 1) and 80% (Case 2) of the examined cells, Conventional cytogenetic techniques (QFQ, CBG, and DA-DAPI), comple mented by fluorescence in situ hybridization studies using alpha satellite probes, showed that both small marker chromosomes (SMCs) primarily consiste d of the centromere and heterochromatin of chromosome 1, a conclusion that was also supported by chromosome 1 painting, In an attempt to establish phe notype-genotype correlations, a further investigation was performed using Y ACs mapped to the chromosome 1 pericentromeric region, A fluorescent signal was evident after hybridization with Y934G9 (1q21) in Case I and Y959C4 (1 p11,1-12) in Case 2, Partial trisomy of unique sequences flanking pericentr omeric sequences is shown to underlie the clinical phenotype in both patien ts. This evidence should be taken into account when SMCs are ascertained, p articularly in prenatal diagnosis, (C) 1999 Wiley-Liss, Inc.