What is Ring Chromosome?- Definition, Mechanism and Abnormalities

What is Ring Chromosome?- Definition, Mechanism and Abnormalities

A ring chromosome is formed when the ends of the same chromosome fuse together and make a ring-like structure. Chromosome ring formation is associated with certain health-related conditions. 

Broad two categorize of chromosome aberrations or chromosome abnormalities are structural and numerical aberrations. When any event alters the structure of a chromosome greatly is referred to as structural chromosomal abnormalities. 

Such conditions are deletions, duplications, translocations, inversions and insertion. Though no one is talking about the “ring chromosome”, it is obviously one of the structural chromosomal defects playing a significant role in many diseases. 

In laymen, a chromosome is an X-shaped structure, linear in nature and has arms. The ring chromosome is round in structure, in which ends of a chromosome have fused. 

This ring isn’t a normal thing and henceforth causes serious to mild health issues for a person or fetus. In this article, we will illustrate how ring chromosome forms, mechanism and principle of ring formation, common ring chromosome syndromes and associated disorders. 

Read more: What is Chromosomal Translocation?- Definition, Mechanism and Types.

What is a ring chromosome? 

When chromosome ends have fused and formed a ring-like structure is known as a ring chromosome, a kind of chromosome aberration. 

The first case of ring chromosome was reported by Lilian Vaughen Morgan in 1926. Although it isn’t a common phenomenon, some ring chromosomes are chromosomes 18, 20 and 22. 

Epilepsy is the common symptom reported in almost all types of ring chromosomes, but the sign, symptoms and severity of the condition depend on which portion gets deleted and how many genes are removed during ring formation. 



The ring chromosome is denoted as “r” in humans here example shows that the ring is formed between p26 to q29. So when you show “r” it indicates a ring chromosome. 

But one may wonder why not all chromosomes form a ring? Why only some? Or why it occurs in some conditions only? 

Structurally, a chromosome has arms, centromere and telomere. Telomeres are the end of chromosomes. It has repetitive DNA sequences located on extreme chromosome ends. 

Their function is to protect genes on arms and serve end replication problems. It is also a kind of protective cap that prevents chromosome fusion. Possibly a protein DNA interaction or protein situated on telomere serve this. 

So telomeres are protective caps that prevent chromosome end fusion, and practically not all chromosomes get fused. 

Mechanism of ring formation: 

Now let us discuss how the chromosome rings form? We have so far explained how telomere prevents ring formation, but some chaotropic events, or random 

Process during cell division removes telomere or deletes telomere. 

So technically, when the telomere, telomeric sequences or telomeric proteins are deactivated, deleted or removed, may induce ring formation, we can say in layman. 

The above explanation is true also, but we need to understand the molecular mechanism behind how this happens. Ring formation occurs via either dsDNA breaks at ends or through dysfunctional telomeres. 

Read more: Chromosome 18 Deletion- Deletion 18p, 18q Distal and 18q Proximal.

dsDNA break at the ends: 

DNA breaks and rejoining occur continuously and simultaneously in our genome. The majority of DNA breaks are repaired by either non-homologous end joining or direct DNA repair. 

When a dsDNA break occurs on the ends of the same chromosome, though highly unlikely, it forms a ring chromosome. A cell’s natural DNA repair mechanism gets a signal to repair the break, possibly a non-homologous end-joining repair mechanism helps in joining the dsDNA breaks of two arms. 

Ends ligate and a ring chromosome forms. 

Interestingly, this happens not only between the two arms of the same chromosome but also between a single-arm too. Unusually, two breakpoints on the same arm occur and form a ring as well. This rare unicentric ring forms in acentric and acrocentric chromosomes. 

When ring chromosomes occur in germ cells and take part in fertilization, the ring inherits in the fetus. Symptoms of the condition depend on the type of ring and on which chromosome it formed. 

What is Ring Chromosome?- Definition, Mechanism and Abnormalities
Mechanism of ring chromosome formation.

Telomere dysfunction:

In the above situation when dsDNA breaks, either some part or whole telomere gets deleted and results in a ring formation. But in this condition, a ring appears by dysfunctioning of telomeres. 

Telomere shortening prevents aging, which means, after every round of replication some DNA from the ends- telomeric sequences are lost. Over time, proteins associated with telomeric DNA are removed or detached. Lack of protective proteins at the telomere makes ends more fusion prone. Consequently, the ends are fused to another chromosome (forms a dicentric chromosome) or on the opposite end of the same chromosome, which ultimately makes a ring! 

Interesting information: 

Epilepsy is the common symptom of ring chromosomes. 

Common ring chromosome abnormalities: 

Ring chromosome 14: 

Ring chromosome 14 or r(14) occurs between the two arms of the same chromosome 14. Only 50 affected patients are reported to date. 

Intellectual disability, seizure, epilepsy, learning problems, developmental delay and motor skill problems are reported. Microcephaly, puffy head and other structural problems are reported as well.

The researcher believes that the severity of the condition depends on the loss of genes during the break. It is a non-inherited genetic trait. A mosaic ring chromosome is also reported in some cases. 

Ring chromosome 20: 

Ring chromosome 20 or r(20) occurs when two broken ends of the same chromosome 20 get rejoined. 

As discussed, a common symptom is an epilepsy and partial seizures cause intellectual and behavioral difficulties later. It is a non-inherited genetic condition and only 60 affected patients reported worldwide. 

Ring chromosome 22: 

The first case of ring chromosome or r(22) was reported in 1970. Chromosome 22 is acrocentric in nature, meaning the p arm is too short, so practically only a few genes are there and nothing lost during ring formation. 

So the symptoms depend on how much portion the distal q arm loses during the event. 

Developmental delay, intellectual disability, autistic behavior, seizure and epilepsy, growth delay are common symptoms reported. The present condition is non-inherited and only a few cases (approximately 100) reported worldwide. 

Summary of the ring chromosome disorders:

Ring chromosome Symptoms 
Ring chromosome 1Structural abnormality, mental retardation and facial abnormality 
Ring chromosome 2Small stature and intellectual disability 
Ring chromosome 3
Ring chromosome 4Craniofacial abnormality 
Ring chromosome 5
Ring chromosome 6Abnormal hands, abnormal facial features and microcephaly 
Ring chromosome 7Speech difficulty and craniofacial abnormalities 
Ring chromosome 8Craniofacial abnormality, abnormal hands and hydronephrosis 
Ring chromosome 9Hypotonia, growth delay and abnormal facial feature 
Ring chromosome 10Intellectual disability, mental retardation, growth delay, reproductive problems and facial dysmorphism. 
Ring chromosome 11
Ring chromosome 12Microcephaly, abnormal facial feature and growth delay 
Ring chromosome 13Microcepathy, reproductive problems and delayed growth 
Ring chromosome 14Varied degree of Mental retardation 
Ring chromosome 15Mental retardation, microcephaly and speech problems 
Ring chromosome 16Mental retardation and growth delay  and facial abnormalities 
Ring chromosome 17
Ring chromosome 18Mental retardation and growth delay  and facial abnormalities 
Ring chromosome 19
Ring chromosome 20Mental retardation and growth delay 
Ring chromosome 21Microcephaly, reproductive failure and short stature 
Ring chromosome 22Autistic like behavior, microcephaly, short stature and intellectual disability 
Ring chromosome XRing chromosome in Turner syndrome 
Ring chromosome Y

Note that with all the above-listed symptoms, varying degrees of epilepsy are commonly reported in all cases. 

Occurrence of ring chromosome: 

The occurrence of ring chromosomes is sporadic in nature, meaning, occur randomly during germ cell formation or differentiation. Also, it is non-inherited and patients don’t have a previous family history of the condition. 

This occurs during germ cell differentiation when some portion of the same chromosome arms are deleted and fused. We have explained the mechanism in this article, elsewhere.  

Ring chromosome and cancer: 

Ring or round or joint chromosome is often observed in most cancer types. And perhaps it may be involved because, after all, the presence of a ring suppresses cell proliferation in tissues it presents. 

Data also suggest that the presence of rings was noticed in most of the invasive cancer and less in benign cancer. We can say, the presence of a ring does do far more damages than we thought. 

The ring present in the case of cancer is totally different. The size of the ring varies even within the same organism and the number may also vary. This meaning, it is highly unstable in case of cancer. 

Here are some of the data showing the prevalence of chromosome rings in different cancers. We are giving fair credit to “atlasofgeneticsoncogoly.com” for providing such important information. 

The information is gathered from their platform. 

Cancer Frequency (%)Cancer Frequency (%) 
Breast 5.7Urinary Bladder 4.5
Colon and rectum 4.6Uterus 2.2
Gallbladder 21.1Meningioma 4.0
Larynx 5.2Acute lymphoblastic leukemia 0.7
Liver 13.0Chronic lymphoblastic leukemia 1.1
Lung 8.8Acute myelogenous leukemia 2.2
Mouth 1.9Osteosarcoma 12.2
Ovary 3.9Mesothelioma 14.2
Pancreas 11.5Malignant fibrous histiocytoma 11.5
Prostate 0Liposarcoma 21.1
skin 3.7Leiomyosarcoma 11.2
Stomach 1.7Ewing’s sarcoma 0.6
Thyroid 1.1Chondrosarcoma 5.6
Uterine cervix 0Chronic myelogenous leukemia 1.0

Note: high frequency of ring chromosome is reported in dermatofibrosarcoma protuberans- 70.3%.

Rings predominantly occur in the genome because of the weak response of the DNA repair mechanism, meaning, cells’ natural DNA repair mechanism can’t repair the break that occurs on chromosome ends. 

Studies suggest that mutation in TP53 (also known as p53) gene which is a potential cancer-causing gene leads to inactivation of repair. 

Karyotyping of ring chromosome:

Ring chromosomes can be detected using the conventional karyotyping technique, however, using FISH to interpret results gives more clarity to results. 

Years of experience and expertise in karyotyping require understanding and interpreting the results of ring chromosomes. Although it is hard to spot ring chromosomes only through karyotyping. 

Ring sometimes occurs with the whole pair of chromosomes and henceforth numerical errors may happen. 

A blood sample, tumor samples or amniotic fluid sample is required to karyotype human, cancer and fetus samples, respectively.   

Wrapping up: 

Ring chromosome abnormalities are heterogeneous in nature, meaning, phenotypes are variable, the origin is unknown and effects are unknown too. The phenotypic variability greatly depends on which chromosome it occurs, the portion deleted or either any chromosome supremacy is involved or not. 

It is also evident that the ring is mitotically insatiable, and imbalanced somatic cell proliferation. The size of the ring may also vary, interestingly larger ring formation is highly associated with growth failure and growth retardation, compared to smaller rings. 

It is also important to indicate here that changes in phenotype are also unknown, the deletions or duplication that cause the phenotypic alteration or the ring itself is still a question to solve. 

Wrapping things up, I can say the chromosome ring and ring formation is a mystery event still not studied thoroughly. The genotypic-phenotypic correlation picture isn’t clear as well. 

Scientists have to go far beyond to solve the mystery of the ring chromosome. 

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