Abstract
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.
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References
Bershteyn M, Hayashi Y, Desachy G, Hsiao EC, Sami S, Tsang KM, Weiss LA, Kriegstein AR, Yamanaka S, Wynshaw-Boris A (2014) Cell-autonomous correction of ring chromosomes in human induced pluripotent stem cells. Nature 507(7490):99–103. https://doi.org/10.1038/nature12923
Burgemeister AL, Daumiller E, Dietze-Armana I, Klett C, Freiberg C, Stark W, Lingen M, Centonze I, Rettenberger G, Mehnert K, Zirn B (2017) Continuing role for classical cytogenetics: Case report of a boy with ring syndrome caused by complete ring chromosome 4 and review of literature. Am J Med Genet A 173(3):727–732. https://doi.org/10.1002/ajmg.a.38063
Callen DF, Eyre HJ, Ringenbergs ML, Freemantle CJ, Woodroffe P, Haan EA (1991) Chromosomal origin of small ring marker chromosomes in man: Characterization by molecular genetics. Am J Hum Genet 48(4):769–782
Chai H, DiAdamo A, Grommisch B, Xu F, Zhou Q, Wen J, Mahoney M, Bale A, McGrath J, Spencer-Manzon M, Li P, Zhang H (2019a) A retrospective analysis of 10-year data assessed the diagnostic accuracy and efficacy of cytogenomic abnormalities in current prenatal and pediatric settings. Front Genet 10:1162. https://doi.org/10.3389/fgene.2019.01162
Chai H, Grommisch B, DiAdamo A, Wen J, Hui P, Li P (2019b) Inverted duplication, triplication and quintuplication through sequential breakage-fusion-bridge events induced by a terminal deletion at 5p in a case of spontaneous abortion. Mol Genet Gen Med 7(10):e00965. https://doi.org/10.1002/mgg3.965
Chai H, Ji W, Wen J, DiAdamo A, Grommisch B, Hu Q, Szekely AM, Li P (2020) Ring chromosome formation by intra-strand repairing of subtelomeric double stand breaks and clinico-cytogenomic correlations for ring chromosome 9. Am J Med Genet A 182(12):3023–3028. https://doi.org/10.1002/ajmg.a.61890
Chai H, Xu F, DiAdamo A, Grommisch B, Mao H, Li P (2022) Cytogenomic characterization of giant ring or rod marker chromosome in four cases of well-differentiated and dedifferentiated liposarcoma. Case Rep Genet 2022:6341207. https://doi.org/10.1155/2022/6341207
Chen H, Tuck-Muller CM, Batista DA, Wertelecki W (1995) Identification of supernumerary ring chromosome 1 mosaicism using fluorescence in situ hybridization. Am J Med Genet 56(2):219–233. https://doi.org/10.1002/ajmg.1320560221
Cote GB, Katsantoni A, Deligeorgis D (1981) The cytogenetic and clinical implications of a ring chromosome 2. Ann Genet 24(4):231–235
Daban JR (2021) Soft-matter properties of multilayer chromosomes. Phys Biol 18(5). https://doi.org/10.1088/1478-3975/ac0aff
de Almeida JC, Llerena JC Jr, Gomes DM, Martins RR, Pereira ET (1983) Ring 13 in an adult male with a 13:13 translocation mother. Ann Genet 26(2):112–115
Gebhart E (2008) Ring chromosomes in human neoplasias. Cytogenet Genome Res 121(3–4):149–173. https://doi.org/10.1159/000138881
Gordon D, Watson A, Desurkar A, Cowley L, Hiemstra TF (2020) Assessing the role of ketogenic dietary therapy in ring chromosome 20 syndrome: A patient-led approach. Epilepsia Open 5(2):295–300. https://doi.org/10.1002/epi4.12387
Gradek GA, Kvistad PH, Houge G (2006) Monosomy 8 rescue gave cells with a normal karyotype in a mildly affected man with 46, XY, r(8) mosaicism. Eur J Med Genet 49(4):292–297. https://doi.org/10.1016/j.ejmg.2005.08.004
Guilherme RS, Meloni VF, Kim CA, Pellegrino R, Takeno SS, Spinner NB, Conlin LK, Christofolini DM, Kulikowski LD, Melaragno MI (2011) Mechanisms of ring chromosome formation, ring instability and clinical consequences. BMC Med Genet 12:171. https://doi.org/10.1186/1471-2350-12-171
Hoo JJ, Obermann U, Cramer H (1974) The behavior of ring chromosome 13. Humangenetik 24(3):161–171. https://doi.org/10.1007/BF00283581
Hook EB (1977) Exclusion of chromosomal mosaicism: Tables of 90%, 95% and 99% confidence limits and comments on use. Am J Hum Genet 29(1):94–97
Hu Q, Chai H, Shu W, Li P (2018) Human ring chromosome registry for cases in the Chinese population: Re-emphasizing cytogenomic and clinical heterogeneity and reviewing diagnostic and treatment strategies. Mol Cytogenet 11(1):19. https://doi.org/10.1186/s13039-018-0367-3
Ki A, Rauen KA, Black LD, Kostiner DR, Sandberg PL, Pinkel D, Albertson DG, Norton ME, Cotter PD (2003) Ring 21 chromosome and a satellited 1p in the same patient: novel origin for an ectopic NOR. Am J Med Genet A 120A(3):365–369. https://doi.org/10.1002/ajmg.a.20236
Kim T, Bershteyn M, Wynshaw-Boris A (2014) Chromosome therapy. Correction of large chromosomal aberrations by inducing ring chromosomes in induced pluripotent stem cells (iPSCs). Nucleus 5(5):391–395. https://doi.org/10.4161/nucl.36300
Kistenmacher ML, Punnett HH, Aronson M, Miller RC, Greene AE, Coriell LL (1975) A ring 9 chromosome. Repository identification no. GM-166. Cytogenet Cell Genet 15(2):122–123. https://doi.org/10.1159/000130508
Kosztolanyi G (1987a) Decreased cell viability of fibroblasts from two patients with a ring chromosome: An in vitro reflection of growth failure? Am J Med Genet 28(1):181–184. https://doi.org/10.1002/ajmg.1320280125
Kosztolanyi G (1987b) Does “ring syndrome” exist? An analysis of 207 case reports on patients with a ring autosome. Hum Genet 75(2):174–179. https://doi.org/10.1007/BF00591082
Kosztolanyi G, Mehes K, Hook EB (1991) Inherited ring chromosomes: An analysis of published cases. Hum Genet 87(3):320–324. https://doi.org/10.1007/BF00200912
Kurtas N, Arrigoni F, Errichiello E, Zucca C, Maghini C, D’Angelo MG, Beri S, Giorda R, Bertuzzo S, Delledonne M, Xumerle L, Rossato M, Zuffardi O, Bonaglia MC (2018) Chromothripsis and ring chromosome 22: A paradigm of genomic complexity in the Phelan-McDermid syndrome (22q13 deletion syndrome). J Med Genet 55(4):269–277. https://doi.org/10.1136/jmedgenet-2017-105125
Ledbetter DH, Riccardi VM, Au WW, Wilson DP, Holmquist GP (1980) Ring chromosome 15: Phenotype, Ag-NOR analysis, secondary aneuploidy, and associated chromosome instability. Cytogenet Cell Genet 27(2–3):111–122. https://doi.org/10.1159/000131472
Li Y, Schwab C, Ryan S, Papaemmanuil E, Robinson HM, Jacobs P, Moorman AV, Dyer S, Borrow J, Griffiths M, Heerema NA, Carroll AJ, Talley P, Bown N, Telford N, Ross FM, Gaunt L, McNally RJQ, Young BD, Sinclair P, Rand V, Teixeira MR, Joseph O, Robinson B, Maddison M, Dastugue N, Vandenberghe P, Stephens PJ, Cheng J, Van Loo P, Stratton MR, Campbell PJ, Harrison CJ (2014) Constitutional and somatic rearrangement of chromosome 21 in acute lymphoblastic leukaemia. Nature 508(7494):98–102. https://doi.org/10.1038/nature13115
Li P, Dupont B, Hu Q, Crimi M, Shen Y, Lebedev I, Liehr T (2022) The past, present, and future for constitutional ring chromosomes: A report of the international consortium for human ring chromosomes. HGG Adv 3(4):100139. https://doi.org/10.1016/j.xhgg.2022.100139
Liehr T (2022) Uniparental disomy is a chromosomic disorder in the first place. Mol Cytogenet 15(1):5. https://doi.org/10.1186/s13039-022-00585-2
Lindsten J, Tillinger K (1962) Self-perpetuating ring chromosome in a patient with gonadal dysgenesis. Lancet 279(7229):593–594. https://doi.org/10.1016/s0140-6736(62)91586-6
Maciejowski J, Li Y, Bosco N, Campbell PJ, de Lange T (2015) Chromothripsis and kataegis induced by telomere crisis. Cell 163(7):1641–1654. https://doi.org/10.1016/j.cell.2015.11.054
Maraschio P, Tupler R, Rossi E, Barbierato L, Uccellatore F, Rocchi M, Zuffardi O, Fraccaro M (1996) A novel mechanism for the origin of supernumerary marker chromosomes. Hum Genet 97(3):382–386. https://doi.org/10.1007/BF02185778
McDermott A, Voyce MA, Romain D (1977) Ring chromosome 4. J Med Genet 14(3):228–232. https://doi.org/10.1136/jmg.14.3.228
Nikitina TV, Menzorov AG, Kashevarova AA, Gridina MM, Khabarova AA, Yakovleva YS, Lopatkina ME, Kizilova EA, Vasilyev SA, Serov OL, Lebedev IN (2018) Generation of two iPSC lines (IMGTi001-A and IMGTi001-B) from human skin fibroblasts with ring chromosome 22. Stem Cell Res 31:244–248. https://doi.org/10.1016/j.scr.2018.08.012
Nussbaum RL, McInnes RR, Willard HF (2001) Thompson & Thompson genetics in medicine, 6th edn. WB Saunders, Philadephia, Pa, London
Petersen MB, Bartsch O, Adelsberger PA, Mikkelsen M, Schwinger E, Antonarakis SE (1992) Uniparental isodisomy due to duplication of chromosome 21 occurring in somatic cells monosomic for chromosome 21. Genomics 13(2):269–274. https://doi.org/10.1016/0888-7543(92)90242-k
Plona K, Kim T, Halloran K, Wynshaw-Boris A (2016) Chromosome therapy: Potential strategies for the correction of severe chromosome aberrations. Am J Med Genet C Semin Med Genet 172(4):422–430. https://doi.org/10.1002/ajmg.c.31530
Pristyazhnyuk IE, Menzorov AG (2018) Ring chromosomes: From formation to clinical potential. Protoplasma 255(2):439–449. https://doi.org/10.1007/s00709-017-1165-1
Rinaldi B, Vaisfeld A, Amarri S, Baldo C, Gobbi G, Magini P, Melli E, Neri G, Novara F, Pippucci T, Rizzi R, Soresina A, Zampini L, Zuffardi O, Crimi M (2017) Guideline recommendations for diagnosis and clinical management of Ring14 syndrome-first report of an ad hoc task force. Orphanet J Rare Dis 12(1):69. https://doi.org/10.1186/s13023-017-0606-4
Rowley J, Muldal S, Lindsten J, Gilbert CW (1964) H3-thymidine uptake by a ring X chromosome in a human female. Proc Natl Acad Sci U S A 51(5):779–786. https://doi.org/10.1073/pnas.51.5.779
Stetten G, Tuck-Muller CM, Blakemore KJ, Wong C, Kazazian HH Jr, Antonarakis SE (1990) Evidence for involvement of a Robertsonian translocation 13 chromosome in formation of a ring chromosome 13. Mol Biol Med 7(6):479–484
Surace C, Berardinelli F, Masotti A, Roberti MC, Da Sacco L, D’Elia G, Sirleto P, Digilio MC, Cusmai R, Grotta S, Petrocchi S, Hachem ME, Pisaneschi E, Ciocca L, Russo S, Lepri FR, Sgura A, Angioni A (2014) Telomere shortening and telomere position effect in mild ring 17 syndrome. Epigenetics Chromatin 7(1):1. https://doi.org/10.1186/1756-8935-7-1
Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131(5):861–872. https://doi.org/10.1016/j.cell.2007.11.019
Tommerup N, Lothe R (1992) Constitutional ring chromosomes and tumour suppressor genes. J Med Genet 29(12):879–882. https://doi.org/10.1136/jmg.29.12.879
Turner B, Jennings AN, den DG, Stapleton T (1962) A self-perpetuating ring chromosome. Med J Aust 49(2):56–58
Wang HC, Melnyk J, Mc DL, Uchida IA, Carr DH, Goldberg B (1962) Ring chromosomes in human beings. Nature 195:733–734. https://doi.org/10.1038/195733a0
Wang Q, Wu W, Xu Z, Luo F, Zhou Q, Li P, Xie J (2015) Copy number changes and methylation patterns in an isodicentric and a ring chromosome of 15q11-q13: Report of two cases and review of literature. Mol Cytogenet 8(1):97. https://doi.org/10.1186/s13039-015-0198-4
Watson A, Watson D, Taylor C (2015) Life with r(20)-Ring chromosome 20 syndrome. Epilepsia 56(3):356-358. https://doi.org/10.1111/epi.12729
Wei Y, Xu F, Li P (2013) Technology-driven and evidence-based genomic analysis for integrated pediatric and prenatal genetics evaluation. J Genet Genomics 40(1):1–14. https://doi.org/10.1016/j.jgg.2012.12.004
Xie X, Chai H, DiAdamo A, Grommisch B, Wen J, Zhang H, Li P (2022) Genotype-phenotype correlations for putative haploinsufficient genes in deletions of 6q26-q27: Report of eight patients and review of literature. Glob Med Genet 9(2):166–174. https://doi.org/10.1055/s-0042-1743568
Xu F, Li L, Schulz VP, Gallagher PG, Xiang B, Zhao H, Li P (2014) Cytogenomic mapping and bioinformatic mining reveal interacting brain expressed genes for intellectual disability. Mol Cytogenet 7(1):4. https://doi.org/10.1186/1755-8166-7-4
Yip MY (2015) Autosomal ring chromosomes in human genetic disorders. Transl Pediatr 4(2):164–174. https://doi.org/10.3978/j.issn.2224-4336.2015.03.04
Zhang HZ, Li P, Wang D, Huff S, Nimmakayalu M, Qumsiyeh M, Pober BR (2004) FOXC1 gene deletion is associated with eye anomalies in ring chromosome 6. Am J Med Genet A 124A(3):280–287. https://doi.org/10.1002/ajmg.a.20413
Zhang HZ, Xu F, Seashore M, Li P (2012) Unique genomic structure and distinct mitotic behavior of ring chromosome 21 in two unrelated cases. Cytogenet Genome Res 136(3):180–187. https://doi.org/10.1159/000336978
Zollino M, Ponzi E, Gobbi G, Neri G (2012) The ring 14 syndrome. Eur J Med Genet 55(5):374–380. https://doi.org/10.1016/j.ejmg.2012.03.009
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Li, P., Liehr, T. (2024). Historical Perspective of Human Ring Chromosomes. In: Li, P., Liehr, T. (eds) Human Ring Chromosomes. Springer, Cham. https://doi.org/10.1007/978-3-031-47530-6_1
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DOI: https://doi.org/10.1007/978-3-031-47530-6_1
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