Medicina Molecular e Genética

The Laws of the Ring: Governing Mechanisms, Diagnostic Standards, and Therapeutic Potentials for Human Constitutional Ring Chromosomes

Abstract

Li P and Hu Q

Human constitutional ring chromosomes are a rare type of chromosome structural abnormalities. The cytogenomic analysis of ring chromosome cases revealed different genomic imbalances and ring structures, variable levels of dynamic mosaicism, and selective karyotype evolution in different tissues. This cytogenomic heterogeneity is likely correlated with variable clinical manifestations of generalized features of ‘ring chromosome syndrome’, chromosome-specific and segmental aneuploidy related phenotypes, and risks of infertility and various types of cancers. Better understanding of the ‘biologic law’ governing ring chromosome formation and its mitotic segregation can contribute to the ‘diagnostic law’ guiding toward best practice in genetic analyses and the ‘therapeutic law’ for evidence-based treatment and management of ring chromosome disorders. Collaborative efforts are needed to study the biological processes involving ring chromosome formation, mitotic segregation and cell-autonomous correction, to develop cytogenomic diagnostic standards, and to generate registry of ring chromosome cases with defined genomic structures and dynamic mosaicism and detailed clinical manifestations. These efforts could provide more reliable karyotype-phenotype correlations for developing chromosome-specific guidelines and recommendations for genetic counseling and clinical treatment.