A Novel de novo Exceptional Complex Chromosomal Rearrangement Involving 5 Chromosomes Resulting in Neurodevelopmental...

Complex chromosomal rearrangements (CCRs) are constitutive structural aberrations involving three or more chromosomal breaks on three or more chromosomes resulting from complex events such as fork stalling and template switching, microhomology-mediated break-induced repair, or breakage-fusion-bridge cycles.

Here we report an 11-year-old female that was referred to our outpatient clinics for learning disability and dysmorphic features. Due to clinical findings, karyotype analysis was done initially, and a CCR involving five chromosomes was detected. Fluorescence in situ hybridization (FISH) analysis and chromosomal microarray analysis were done subsequently. Balanced translocations were observed between chromosomes 1, 5, 7, and 10, a balanced paracentric inversion of chromosome 2, and two interstitial deletions in the long arm of the chromosome 5. Optical genome mapping was done to further investigate this exceptional CCR and a paracentric inversion that was associated with the two interstitial deletions was detected in the long arm of chromosome 5.

Molecular cytogenetic techniques, such as microarray and FISH, are essential for detecting copy number variations at CCRs that appear to be balanced by karyotyping. Nonetheless, optical genome mapping enhances the resolution offering a valuable complement to traditional cytogenetic techniques.