Apparently balanced chromosomal rearrangements (ABCR) are associated with an abnormal phenotype in 6 % of cases. This may be due to the disruption of genes at the breakpoint. However, conventional methods of breakpoint cloning are laborious and time-consuming. Here, we used whole-genome next-generation sequencing (NGS) to rapidly locate breakpoints at the molecular level in four patients with multiple congenital abnormalities and/or intellectual deficiency that were carrying ABCR (1 translocation, 1 complex chromosomal rearrangement and 2 inversions).

We were able to map all the breakpoints. We showed that five genes were disrupted (TCF4, SHANK2, PPFIA1, RAB19, KCNQ1), that could account for the phenotype in three patients.

So, we suggest that patients with ABCR and abnormal phenotype should be investigated by NGS. (By Dr Caroline Schluth-Bolard, http://jmg.bmj.com/content/early/2013/01/11/jmedgenet-2012-101351 )