Prenatal diagnosis of chromothripsis, with nine breaks characterized by karyotyping, FISH, microarray and whole‐genome sequencing

What's already known about this topic? Chromothripsis is a recently described phenomenon whereby a single catastrophic event leads to multiple chromosome breaks and subsequent repair through nonhomologous end joining. The result can present karyotypically as a complex rearrangement and occurs both congenitally and in cancer cells. What does this study add? We report, to our knowledge, the first case of congenital chromothripsis uncovered prenatally through a combination of G‐banded karyotype analysis and whole‐genome sequencing by jumping libraries. The G‐banded karyotype initially suggested the involvement of five chromosomes and six breakpoints. Whole‐genome sequencing further resolved this event to include nine total breakpoints that disrupt seven independent genes, all in the presence of a normal microarray result. This emphasizes the complementarity that whole‐genome sequencing can provide to the initial karyotype analysis as a reflex test when a rearrangement is detected. We also discuss the dilemma of prognosis with this finding.