Tandem duplication/deletion in a maternally derived chromosome 9 supernumerary derivative resulting in 9p trisomy and partial 9q tetrasomy

A le-week stillborn female fetus with bilateral cleft palate, horseshoe kid ney, bicornuate uterus, low-set ears, and intrauterine growth retardation ( IUGR) was found to have a supernumerary derivative chromosome 9 (der(9)) wi th an apparent tandem duplication in the long arm. PCR analysis at five pol ymorphic loci confirmed the duplication and showed an adjacent deletion, wh ile whole chromosome FISH demonstrated only chromosome 9 to be involved. Fu rther FISH studies of der(9) found the 9qh region to be duplicated, telomer ic sequences to be intact, and subtelomeric sequences to be absent. Thus, t he fetus was determined to be trisomic for 9pter-->9q12 and 9q34.3-->9qter, tetrasomic for 9q12-->9q33, and disomic for 9q33-->9q34.3. These results a re consistent with a tandem duplication of 9q12-->9q33 and adjacent distal deletion as designated by the karyotype, 47,XX,+der(9)dup(9)(q12q33)del(9) (q33q34.3),ish der(9) (WCP9+,D9Z1x2,STP9q-, AHT+) de novo, In addition to c haracterizing der(9), the combined PCR and cytogenetic studies refined the Genome Database Map of three loci (D9S907, D9S155, and D9S302) approximatel y to the distal 9q33 region. Without the attempt to refine breakpoints by P CR analysis, the deletion in distal 9q would not have been detected. Tandem direct duplication/deletion chromosomes have been reported in fewer cases than inverted duplication/deletions. We propose mechanisms of origin, consi stent with those for recurrent interstitial microdeletion and microduplicat ion syndromes, shown to arise by recombination at homologous, flanking DNA sequences. (C) 2000 Wiley-Liss, Inc.