Ring chromosomes: from formation to clinical potential

Abstract

Ring chromosomes (RCs) are circular DNA molecules, which occur rarely in eukaryotic nuclear genomes. Lilian Vaughan Morgan first described them in the fruit fly. Human embryos very seldom have RCs, about 1:50,000. Carriers of RCs may have varying degrees of symptoms, from healthy phenotype to serious pathologies in physical and intellectual development. Many authors describe common symptoms of RC presence: short stature and some developmental delay that could be described as a "ring chromosome syndrome." As a rule, RCs arise de novo through the end-joining of two DNA double-strand breaks, telomere-subtelomere junction, or inv dup del rearrangement in both meiosis and mitosis. There are family cases of RC inheritance. The presence of RCs causes numerous secondary chromosome rearrangements in vivo and in vitro. RCs can change their size, become lost, or increase their copy number and cause additional deletions, duplication, and translocations, affecting both RCs and other chromosomes. In this review, we examine RC inheritance, instability, mechanisms of formation, and potential clinical applications of artificially created RCs for large-scale chromosome rearrangement treatment.

Clinical, cytogenetic, and molecular findings in a patient with ring chromosome 4: case report and literature review

“…Ring chromosome formation has been described by different mechanisms [1][2][3][4][5]. The ring chromosome 4 in our patient presents a terminal deletion with duplication resulting from inv dup del rearrangement [52]. This deletion and duplication is caused by homologous recombination between duplicated segments near the breakpoints, allowing telomere healing and telomere capture with the formation of an intermediate dicentric chromosome [2,52].…”

A Familial Small Supernumerary Marker Chromosome 15 Associated with Cryptic Mosaicism with Two Different Additional Marker Chromosomes Derived de novo from Chromosome 9: Detailed Case Study and Implications for Recurrent Pregnancy Loss

“…It seems likely that the observed derivatives of chromosome 9 in the proband also indicate ring chromosome instability. Indeed, the origin of the 4 centromere-specific regions in ring chromosome 9 may be explained by an odd-numbered series of sister chromatid exchanges during S phase, leading to a doubling in size of the ring chromosome and an increase in centromere number [Pristyazhnyuk and Menzorov, 2018].…”

Getting to grips with circular chromosomes

“…The work of Wu et al provides new insights into how chromosomes fuse together and how telomeres are maintained independently from the telomerase enzyme. Moreover, the findings from this study might go beyond yeast and improve our understanding of various human medical syndromes caused by the ends of chromosomes fusing to form ring shapes ( Pristyazhnyuk and Menzorov, 2018 ).…”