SNP Array and Genome Sequencing Demonstrated Revertant Mosaicism via Postzygotic Rescue as the Main Mechanism of Mosaic Chromosomal Terminal Duplications

INTRODUCTION
• Trisomy rescue is a well-known mechanism of generating a normal cell line. Here, we describe revertant mosaicism, in which all cells initially carry chromosomal structural rearrangement instead of aneuploidy, and a subset reverts to normal cells without rearrangement – resulting in a mosaic population composed of both abnormal and genetically corrected cells.
• Recognizing this mechanism reframes how we interpret mosaic structural variation in rare diseases.
• Mosaicism for a normal cell population and a pure terminal duplication is extremely rare.
• We previously reported two siblings with features of Down syndrome and mosaicism for an inherited chromosome 8 with additional chromosome 21 material attached to the end of 8q; interstitial telomeric sequences (ITS) were present at the junction. The normal cells are proposed to arise through a reversion of the abnormal chromosome 8 due to ITS instability.
• In this study, we further investigated the formation mechanism of mosaic chromosomal rearrangements.