Fig. 2.

A complex DEL-INV-DEL rearrangement identified by WGS causes severe epilepsy. a Screenshot of the deletions and inversion from the Integrative Genomics Viewer (IGV) in individual RD_P393. Short-read whole-genome sequencing (WGS) detected two clustered deletions of 630 kb (SCN3A, SCN2A, CSRNP3, GALNT3) and 121 kb (SCN1A), respectively. The genomic segment of normal copy number state in-between the deletions (139 kb, TTC21B) had been inverted. Both inversion breakpoint junctions are shown with the green and blue bars corresponding to discordant reads with mates located on the other side of the inversion. b Screenshot of DEL-INV-DEL rearrangement confirmed by array comparative genomic hybridization (array-CGH). Screenshot from the Cytosure Interpret Software. The deletions in the rearrangement were confirmed using array-CGH. c Breakpoint junction sequences. Sequence analysis of the breakpoint junctions revealed insertions in both junctions of 38 bp and 59 bp, respectively (pink). Substantial parts of the insertions had been templated from sequences involved in the rearrangement (underlined), suggestive of a replicative error as the underlying mechanism of formation. L1 repetitive elements were present in two of the breakpoints but did not form any fusion L1 elements. Lowercase letters indicate deleted sequences