Short-read Genome sequencing (sr-GS) affords efficient characterization of apparently balanced chromosomal rearrangement. However, 9 to 11% of cases remain undetectable, mainly due to highly repetitive genomic regions at breakpoints. We studied 14 patients with abnormal phenotype carrying ABCR that could not be detected by sr-GS. We used a combination of different approaches including fluorescence in situ hybridisation and long fragment based techniques. In half of cases, the breakpoints resulted in a deleterious effect on a pathogenic gene, explaining patient’s phenotype. The resolution of chromosomal rearrangements involving repetitive regions is thus essential to patients’ care. (By Pr Caroline Schluth-Bolard, https://jmg.bmj.com/content/early/2025/08/20/jmg-2025-110838 )