Unique DUP-TRP/INV-DUP Structure Detected by Long-Read Sequencing

Duplication-triplication/inverted-duplication (DUP-TRP/INV-DUP) is one of the mechanisms that causes genomic triplications. There are some characteristics of the DUP-TRP/INV-DUP; the appearance of a moving average of signal log2 ratio in genomic copy number analysis consisting of the highest center with lower steps on both sides; the chromosomal structure is composed of only two junctions; there are inverted repeats at the ends of the triplications and duplications on the same side and those connected in the opposite direction; and the size of the DUP-TRP/INV-DUP structure is generally less than the 1-Mb range. In this study, we analyzed two patients with DUP-TRP/INV-DUP involving PLP1 and MECP2. Whole-genome long-read sequencing was performed, and all breakpoint junctions were confirmed. Patient 1 showed a typical DUP-TRP/INV-DUP pattern involving PLP1, whereas Patient 2 showed a unique DUP-TRP/INV-DUP pattern in the MECP2 region, which involved additional chromosomal breakages at a 46-Mb far remote region of Xq22.3. Based on this finding, we suspected that chromosomal breakage at Xq22.3 was the initial damage. The detected two break ends were considered to be repaired by binding to the Xq28 region adjacent to the inverted repeat structure to form a triplication structure.