{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T09:24:40Z","timestamp":1793006680360,"version":"4.5.0"},"reference-count":26,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T00:00:00Z","timestamp":1750809600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Ring chromosomes (RCs) can be rare or common depending on the chromosome involved. With interest in the historical RCs identified by our laboratory, we curated instances to provide further information to this research field. Methodology: We carried out a retrospective, single-center study of constitutional RCs identified starting in the late 1980s. Details for 40 RCs with a modal number of 46 chromosomes are featured here. Results: Mosaic and non-mosaic RCs are identified, with a preponderance of pediatric-aged females at first ascertainment. We corroborated an enrichment for acrocentric and X chromosome RCs. Six were ascertained perinatally, with peripheral blood being the most commonly studied postnatal specimen type. Notable RCs included a female fetus with an increased risk for monosomy X, whose mosaic RCY arose secondary to a translocation between the sex chromosomes. In another, a series of complex events formed three structurally aberrant chromosomes, including an RC4 with loss of 4p16.3, corresponding with the observed phenotypic expression of Wolf\u2013Hirschhorn syndrome. In another, a mosaic RCX was co-identified with an isochromosome 21q, resulting in a dual diagnosis of trisomy 21 and Turner syndrome. In another, the atypical RC21 structure raises the possibility of a complex rearrangement. Chromosomal microarray data clarified breakpoints and gene dosage imbalances in fifteen, while low-level mosaicism for the RC escaped detection by array in another. Eight RCs were de novo, and parental exclusion was documented for six. Conclusions: This study illustrates the need for cytogenomic follow-up to improve the literature for patients with RCs.<\/jats:p>","DOI":"10.3390\/genes16070736","type":"journal-article","created":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T05:29:58Z","timestamp":1751002198000},"page":"736","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Characterization of Constitutional Ring Chromosomes over 37 Years of Experience at a Single-Site Institution"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9879-427X","authenticated-orcid":false,"given":"Jaclyn B.","family":"Murry","sequence":"first","affiliation":[{"name":"Greenwood Genetic Center, 101 Gregor Mendel Circle, Greenwood, SC 29646, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara R.","family":"DuPont","sequence":"additional","affiliation":[{"name":"Greenwood Genetic Center, 101 Gregor Mendel Circle, Greenwood, SC 29646, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,25]]},"reference":[{"key":"ref_1","first-page":"100139","article-title":"The Past, Present, and Future for Constitutional Ring Chromosomes: A Report of the International Consortium for Human Ring Chromosomes","volume":"3","author":"Li","year":"2022","journal-title":"HGG Adv."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1159\/000129710","article-title":"Chromosomal Mosaic in a Girl with Some Features of Mongolism","volume":"1","author":"Lindsten","year":"1962","journal-title":"Cytogenetics"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Li, P., and Liehr, T. (2024). Historical Perspective of Human Ring Chromosomes. Human Ring Chromosomes: A Practical Guide for Clinicians and Families, Springer International Publishing.","DOI":"10.1007\/978-3-031-47530-6"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2693","DOI":"10.1016\/j.ajhg.2024.10.006","article-title":"Resolution of Ring Chromosomes, Robertsonian Translocations, and Complex Structural Variants from Long-Read Sequencing and Telomere-to-Telomere Assembly","volume":"111","author":"Mostovoy","year":"2024","journal-title":"Am. J. Hum. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s13039-018-0367-3","article-title":"Human Ring Chromosome Registry for Cases in the Chinese Population: Re-Emphasizing Cytogenomic and Clinical Heterogeneity and Reviewing Diagnostic and Treatment Strategies","volume":"11","author":"Hu","year":"2018","journal-title":"Mol. Cytogenet."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Liehr, T., and Li, P. (2024). A New Database on Constitutional Human Ring Chromosomes, OBM Genetics, Springer.","DOI":"10.1007\/978-3-031-47530-6"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Li, P., and Liehr, T. (2024). Ring Chromosome 4. Human Ring Chromosomes: A Practical Guide for Clinicians and Families, Springer International Publishing.","DOI":"10.1007\/978-3-031-47530-6"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Li, P., and Liehr, T. (2024). Ring Chromosome 13. Human Ring Chromosomes: A Practical Guide for Clinicians and Families, Springer International Publishing.","DOI":"10.1007\/978-3-031-47530-6"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Li, P., and Liehr, T. (2024). Ring Chromosome 14. Human Ring Chromosomes: A Practical Guide for Clinicians and Families, Springer International Publishing.","DOI":"10.1007\/978-3-031-47530-6"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1002\/ajmg.10207","article-title":"Further Delineation of the Chromosome 14q Terminal Deletion Syndrome","volume":"110","author":"Quik","year":"2002","journal-title":"Am. J. Med. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Li, P., and Liehr, T. (2024). Ring Chromosome 15. Human Ring Chromosomes: A Practical Guide for Clinicians and Families, Springer International Publishing.","DOI":"10.1007\/978-3-031-47530-6"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Li, P., and Liehr, T. (2024). Ring Chromosome 18. Human Ring Chromosomes: A Practical Guide for Clinicians and Families, Springer International Publishing.","DOI":"10.1007\/978-3-031-47530-6"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1002\/1096-8628(20010701)101:3<226::AID-AJMG1349>3.0.CO;2-#","article-title":"Clinical and Molecular-Cytogenetic Studies in Seven Patients with Ring Chromosome 18","volume":"101","author":"Stankiewicz","year":"2001","journal-title":"Am. J. Med. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1002\/ajmg.10059","article-title":"First Familial Case of Ring Chromosome 18 and Monosomy 18 Mosaicism","volume":"104","author":"Yardin","year":"2001","journal-title":"Am. J. Med. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Li, P., and Liehr, T. (2024). Ring Chromosome 21. Human Ring Chromosomes: A Practical Guide for Clinicians and Families, Springer International Publishing.","DOI":"10.1007\/978-3-031-47530-6"},{"key":"ref_16","first-page":"965401","article-title":"Monosomy 21 Seen in Live Born Is Unlikely to Represent True Monosomy 21: A Case Report and Review of the Literature","volume":"2014","author":"Burgess","year":"2014","journal-title":"Case Rep. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/j.annder.2019.01.023","article-title":"Alopecia, deformed ear and mental retardation associated with terminal 21q deletion","volume":"146","author":"Lafabregue","year":"2019","journal-title":"Ann. Dermatol. Venereol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/j.cell.2011.07.042","article-title":"Chromosome Catastrophes Involve Replication Mechanisms Generating Complex Genomic Rearrangements","volume":"146","author":"Liu","year":"2011","journal-title":"Cell"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Li, P., and Liehr, T. (2024). Ring Chromosome 22. Human Ring Chromosomes: A Practical Guide for Clinicians and Families, Springer International Publishing.","DOI":"10.1007\/978-3-031-47530-6"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/ng1933","article-title":"Mutations in the Gene Encoding the Synaptic Scaffolding Protein SHANK3 Are Associated with Autism Spectrum Disorders","volume":"39","author":"Durand","year":"2007","journal-title":"Nat. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1136\/jmedgenet-2011-100225","article-title":"Association between Deletion Size and Important Phenotypes Expands the Genomic Region of Interest in Phelan-McDermid Syndrome (22q13 Deletion Syndrome)","volume":"48","author":"Sarasua","year":"2011","journal-title":"J. Med. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Li, P., and Liehr, T. (2024). Ring Chromosome X. Human Ring Chromosomes: A Practical Guide for Clinicians and Families, Springer International Publishing.","DOI":"10.1007\/978-3-031-47530-6"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Li, P., and Liehr, T. (2024). Ring Chromosome Y. Human Ring Chromosomes: A Practical Guide for Clinicians and Families, Springer International Publishing.","DOI":"10.1007\/978-3-031-47530-6"},{"key":"ref_24","first-page":"71","article-title":"Molecular Analysis of Ring y Chromosome in a 10-Year-Old Boy with Mixed Gonadal Dysgenesis and Growth Hormone Deficiency","volume":"14","author":"Milenkovic","year":"2011","journal-title":"Balk. J. Med. Genet. BJMG"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1744.e1","DOI":"10.1016\/j.fertnstert.2005.06.034","article-title":"Mosaic Ring Y Chromosome in Two Normal Healthy Men with Azoospermia","volume":"84","author":"Bertini","year":"2005","journal-title":"Fertil. Steril."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1002\/1096-8628(20000828)93:5<343::AID-AJMG1>3.0.CO;2-0","article-title":"Novel Ring Chromosome Composed of X- and Y-Derived Material in a Girl with Manifestations of Ullrich-Turner Syndrome","volume":"93","author":"Grass","year":"2000","journal-title":"Am. J. Med. Genet."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/16\/7\/736\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:58:40Z","timestamp":1760032720000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/16\/7\/736"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,25]]},"references-count":26,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["genes16070736"],"URL":"https:\/\/doi.org\/10.3390\/genes16070736","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,25]]}}}