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. [ABSTRACT FROM AUTHOR]