Fig. 1

Overview of complex chromosomal rearrangements in the patient with MCA/MR and study design. a The breakpoint locations and genomic rearrangements on the four affected chromosomes in the germline chromothripsis patient determined by mate-pair and breakpoint fusion sequencing. Inversions are depicted with dashed lines beneath the derivative chromosomes. The four deleted fragments are shown below the derivative chromosomes. This illustration is adapted from van Heesch et al. [19]. b Overview of the experimental setup of this study. Molecular effects of the chromosomal rearrangements on deleted, truncated, and fused genes and genes within 1 Mb of the rearrangements were determined by trio-based RNA-seq of iPSCs and iPSC-derived neuronal cells from the patient and both parents. These data were compared with previously generated expression data of blood samples of the patient and parents to identify molecular phenotypes that contribute to the patient’s phenotype but are not detectable in blood [19]