MOLECULAR MAPPING OF THE EDWARDS-SYNDROME PHENOTYPE TO 2 NONCONTIGUOUS REGIONS ON CHROMOSOME-18

In an effort to identify regions on chromosome 18 that may be critical in the appearance of the Edwards syndrome phenotype, we have analyzed six patients with partial duplication of chromosome 18. Four of the p atients have duplications involving the distal half of 18q (18q21.1-qt er) and are very mildly affected. The remaining two patients have most of 18q (18q12.1-qter) duplicated, are severely affected, and have bee n diagnosed with Edwards syndrome. We have employed FISH, using DNA pr obes from a chromosome 18-specific library, for the precise determinat ion of the duplicated material in each of these patients. The clinical features and the extent of the chromosomal duplication in these patie nts were compared with four previously reported partial trisomy 18 pat ients, to identify regions of chromosome 18 that may be responsible fo r certain clinical features of trisomy 18. The comparative analysis co nfirmed that there is no single region on 18q that is sufficient to pr oduce the trisomy 18 phenotype and identified two regions on 18q that may work in conjunction to produce the Edwards syndrome phenotype. In addition, correlative analysis indicates that duplication of 18q12.3-q 22.1 may be associated with more severe mental retardation in trisomy 18 individuals.