CYTOGENETIC AND MOLECULAR CHARACTERIZATION OF INVERTED DUPLICATED CHROMOSOMES 15 FROM 11 PATIENTS

We have studied the inverted duplicated chromosomes 15 (inv dup(15)) f rom 11 individuals-7 with severe mental retardation and seizures, 3 wi th a normal phenotype, and I with Prader-Willi syndrome (PWS). Through a combination of FISH and quantitative DNA analyses, three different molecular sizes of inv dup(15) were identified. The smallest inv dup(1 5) was positive only for the centromeric locus D15Z1 (type 1); the nex t size was positive for D15Z1 and D15S18 (type 2); and the largest inv dup(15) was positive for two additional copies of loci extending from D15Z1 and D15S18 through D15S12 (type 3). Type 1 or type 2 was observ ed in the three normal individuals and the PWS patient. Type 3 was obs erved in all seven individuals with mental retardation and seizures bu t without PWS or Angelman Syndrome (AS). The PWS patient, in addition to being mosaic for a small inv dup(15), demonstrated at D15S63 a meth ylation pattern consistent with maternal uniparental inheritance of th e normal chromosomes 15. The results from this study show (a) two addi tional copies of proximal 15q loci, D15S9 through D15S12, in mentally retarded patients with an inv dup(15) but without AS or PWS and (b) no additional copies of these loci in patients with a normal phenotype o r with PWS.