Background: . This study reports the identification of TDD in 2 unrelated families using long-read HiFi genome sequencing (GS), which uncovered homozygous deletions missed by conventional next-generation sequencing (NGS). Methods: Long-read HiFi GS was performed on blood-derived genomic DNA from affected individuals in both families using the Revio system (Pacific Biosciences). Results: element and distinct retrotransposon subclasses: ERV1 in family 1 and L1MB8 in family 2. The lack of extended homology at breakpoint junctions, deletion sizes, and the dense repetitive genomic architecture support a replication-based rearrangement mechanism, most consistent with fork stalling and template switching or microhomology-mediated break-induced repair (FoSTeS/MMBIR). Discussion: deletions, elucidating the mechanistic underpinnings of genomic instability at this locus. Finally, these results suggest that TDD prevalence may be underestimated because of undetected SVs.
Sabbagh et al. (Mon,) studied this question.