Diagnostic Methods for Ring Chromosomes

The molecular characterization of ring chromosome (RC) structural aberrations requires the use of cytogenomic techniques. The first RCs were characterized by the analysis of non-banded chromosomes and quinacrine fluorescent dye. G-banding, fluorescence in situ hybridization (FISH), and chromosome microarray analysis (CMA) have been used to identify the chromosome origin of the ring, the degree of mosaicism, the regions deleted and/or gained from the RC, and the dynamic mosaicism present in each patient. RCs in CMA often appear as one chromosome with terminal deletions or additional material around the pericentromeric region of a chromosome. Other molecular techniques have been used to distinguish which chromosome is involved in the ring and which regions are present or missing from the RC. Next-generation sequencing (NGS) will define the joint sequences from both the short arms and long arms to reveal ring formation mechanisms. Optical genome mapping (OGM), a new technology not yet standard in many cytogenomic laboratories, has been used to identify the chromosome of origin, the ring structure and the sequences lost and gained from the ring, and the mosaicism present in a single analysis. Integrated cytogenomic analyses should be recommended and performed to define the chromosomal structure, cellular dynamic mosaicism, genomic imbalance, and rearrangement in RCs in current diagnostic practice.