Inverted tandem (“mirror”) duplications in human chromosomes: Inv dup 8p, 4q, 22q

We have studied 4 patients with inverted tandem duplications of parts of chromosomes, a hitherto rarely identified from of a structural rearrangement involving a single chromosome in man. In Patients 1 and 2, the duplication involved parts of the short arm of chromosome 8 (regions 8p 12→8p23 and 8p21→8p23, respectively). Both patients manifested certain characteristics of the mosaic trisomy 8 syndrome. Elevated levels of glutathione reductase (GSR) in their erythrocytes supported the interpretation of a partial duplication of chromosome 8 and indicated a regional localization for the GSR gene locus. In Patient 3, the distal half of the long arm of chromosome 4 was duplicated (region4q26→4q35). Clinical evidence supported this interpretation, as Patient 3 resembled phenotypically the 13 reported cases with duplication of the distal 4q. The cytogenetic findings in Patient 4 suggested a possibly inverted duplication of 22q. The clinical correlation was less convincing due to the lack of a well-defined phenotype for trisomy 22. These chromosome aberrations had occurred de novo in all 4 cases. Although they involved different chromosomal regions, they might well have arisen by the same mechanism. Possible modes of origin that are discussed in detail include unequal exchange between homologous chromosomes, between chromatids of 1 chromosome or between strands of 1 DNA duplex.