CYTOGENETIC AND MOLECULAR ANALYSIS OF INV-DUP(15) CHROMOSOMES OBSERVED IN 2 PATIENTS WITH AUTISTIC DISORDER AND MENTAL-RETARDATION

A variety of distinct phenotypes has been associated with supernumerar y inv dup(15) chromosomes. Although different cytogenetic rearrangemen ts have been associated with distinguishable clinical syndromes, preci se genotype-phenotype correlations have not been determined. However, the availability of chromosome 15 DNA markers provides a means to char acterize inv dup(15) chromosomes in detail to facilitate the determina tion of specific genotype-phenotype associations. The describe 2 patie nts with an autistic disorder, mental retardation, developmental delay , seizures, and supernumerary inv dup(15) chromosomes. Conventional an d molecular cytogenetic studies confirmed the chromosomal origin of th e supernumerary chromosomes and showed that the duplicated region exte nded to at least band 15q13. An analysis of chromosome 15 microsatelli te CA polymorphisms suggested a maternal origin of the inv dup(15) chr omosomes and biparental inheritance of the two intact chromosome 15 ho mologs. The results of this study add to the existing literature which suggests that the clinical phenotype of patients with a supernumerary inv dup(15) chromosome is determined not only by the extent-of the du plicated region, but by the dosage of genes located within band 15q13 and the origin of-the normal chromosomes 15. (C) 1996 Wiley-Liss, Inc.