Historical Perspective of Human Ring Chromosomes

Human ring chromosomes (RCs) are a rare type of chromosomal structural abnormality. Current cytogenomic analysis revealed heterogeneous genomic rearrangements in the ring structures, variable levels of dynamic mosaicism, and selective karyotype evolution in various tissues. This cytogenomic heterogeneity is likely correlated with variable clinical heterogeneity ranging from generalized features of ‘ring syndrome’, chromosome-specific and segmental aneuploidy related phenotypes, to risks of infertility and various types of cancers. Better understanding of the molecular mechanisms governing RC formation and its mitotic behavior can contribute toward best practice in comprehensive cytogenomic analyses and evidence-based treatment and management for affected patients of RCs. Collaborative efforts for systematic evidence review on cases of specific RCs, close interaction with patient advocate organization (PAO), and an online registry of ring chromosome cases are undertaken by an International Consortium of Human Ring Chromosomes (ICHRC). These efforts are aimed to develop chromosome-specific guidelines and recommendations in laboratory diagnosis and genetic counseling and provide more reliable clinico-cytogenomic correlations for clinical management and treatment for patients of RCs.