Ring chromosomes have been described for all human chromosomes and are typically associated with physical and/or mental abnormalities resulting from a deletion of the terminal ends of both chromosome arms. This report describes the presence of a ring chromosome 9 in a 2-year-old male child associated with developmental delay. The proband manifested a severe phenotype comprising facial dysmorphism, congenital heart defects, and seizures. The child also exhibited multiple cell lines with mosaic patterns of double rings, a dicentric ring and loss of the ring associated with mitotic instability and dynamic tissue-specific mosaicism. His karyotype was 46,XY,r(9)(p22q34)[89]/46,XY,dic r(9; 9)(p22q34;p22q34)[6]/45, XY,-9[4]/47,XY,r(9),+r(9)[1]. However, the karyotypes of his parents and elder brother were normal. FISH using mBAND probe and subtelomeric probes specific for p and q arms for chromosome 9 showed no deletion in any of the regions. Chromosomal microarray analysis led to the identification of a heterozygous deletion of 15.7 Mb from 9p22.3 to 9p24.3. The probable role of the deleted genes in the manifestation of the phenotype of the proband is discussed.

1.
Ali BR, Silhavy JL, Gleeson MJ, Gleeson JG, Al-Gazali L: A missense founder mutation in VLDLR is associated with dysequilibrium syndrome without quadrupedal locomotion. BMC Med Genet 13:80 (2012).
2.
Arnedo N, Nogués C, Bosch M, Templado C: Mitotic and meiotic behaviour of a naturally transmitted ring Y chromosome: reproductive risk evaluation. Hum Reprod 20:462-468 (2005).
3.
Barbaro M, Balsamo A, Anderlid BM, Myhre AG, Gennari M, et al: Characterization of deletions at 9p affecting the candidate regions for sex reversal and deletion 9p syndrome by MLPA. Eur J Hum Genet 17:1439-1447 (2009).
4.
Boycott KM, Flavelle S, Bureau A, Glass HC, Fujiwara TM, et al: Homozygous deletion of the very low density lipoprotein receptor gene causes autosomal recessive cerebellar hypoplasia with cerebral gyral simplification. Am J Hum Genet 77:477-483 (2005).
5.
Caba L, Rusu C, Plăiaşu 5th, Gug G, Grămescu M, et al: Ring autosomes: some unexpected findings. Balkan J Med Genet 15:35-46 (2012).
6.
Cote GB, Katsantoni A, Deligeorgis D: The cytogenetic and clinical implication of a ring chromosome 2. Ann Genet 24:231-235 (1981).
7.
Faas BH, de Leeuw N, Mieloo H, Bruinenberg J, de Vries BB: Further refinement of the candidate region for monosomy 9p syndrome. Am J Med Genet A 143A:2353-2356 (2007).
8.
Fisher SE: Dissection of molecular mechanisms underlying speech and language disorders. Appl Psycholinguist 26:111-128 (2005).
9.
Griggs BL, Ladd S, Saul RA, DuPont BR, Srivastava AK: Dedicator of cytokinesis 8 is disrupted in two patients with mental retardation and developmental disabilities. Genomics 91:195-202 (2008).
10.
Guilherme RS, Meloni VF, Kim CA, Pellegrino R, Takeno SS, et al: Mechanisms of ring chromosome formation, ring instability and clinical consequences. BMC Med Genet 12:171 (2011).
11.
Hauge X, Raca G, Cooper S, May K, Spiro R, et al: Detailed characterization of, and clinical correlations in, 10 patients with distal deletions of chromosome 9p. Genet Med 10:599-611 (2008).
12.
Hungerford DA: Leukocytes cultured from small inocula of whole blood and the preparation of metaphase chromosomes by treatment with hypotonic KCl. Stain Technol 40:333-338 (1965).
13.
Ikeuchi T, Sasaki T: Accumulation of early mitotic cells in ethidium bromide-treated human lymphocyte cultures. Proc Jpn Acad 55:15-18 (1979).
14.
ISCN 2013. An International System for Human Cytogenetic Nomenclature; in Shaffer LG, McGowan-Jordan J, Schmid M (eds) (Karger, Basel 2013).
15.
Kadotani T, Watanabe Y, Kiyuna T, Kawamoto T, Takemura I, et al: A case of 46,XX/46,XX,r(9) with severe mental retardation. Proc Jpn Acad 56(B):85-88 (1980).
16.
Kawara H, Yamamoto T, Harada N, Yoshiura K, Niikawa N, et al: Narrowing candidate region for monosomy 9p syndrome to a 4.7-Mb segment at 9p22.2-p23. Am J Med Genet A 140:373-377 (2006).
17.
Knijnenburg J, van Haeringen A, Hansson KB, Lankester A, Smit MJ, et al: Ring chromosome formation as a novel escape mechanism in patients with inverted duplication and terminal deletion. Eur J Hum Genet 15:548-555 (2007).
18.
Kosztolányi G: Does ‘ring syndrome' exist? An analysis of 207 case reports on patients with a ring autosome. Hum Genet 75:174-179 (1987).
19.
Lerer I, Sagi M, Meiner V, Cohen T, Zlotogora J, et al: Deletion of the ANKRD15 gene at 9p24.3 causes parent-of-origin-dependent inheritance of familial cerebral palsy. Hum Mol Genet 14:3911-3920 (2005).
20.
Pezzolo A, Gimelli G, Cohen A, Lavaggetto A, Romano C, et al: Presence of telomeric and subtelomeric sequences at the fusion points of ring chromosomes indicates that the ring syndrome is caused by ring instability. Hum Genet 92:23-27 (1993).
21.
Purandare SM, Lee J, Hassed S, Steele MI, Blackett PR, et al: Ring chromosome 9 [r(9)(p24q34)]: a report of two cases. Am J Med Genet Part A 138A:229-235 (2005).
22.
Rossi E, Riegel M, Messa J, Gimelli S, Maraschio P, et al: Duplications in addition to terminal deletions are present in a proportion of ring chromosomes: clues to the mechanisms of formation. J Med Genet 45:147-154 (2008).
23.
Seabright M: A rapid banding technique for human chromosomes. Lancet 2:971-972 (1971).
24.
Sibbesen EC, Jespersgaard C, Alosi D, Bisgaard AM, Tümer Z: Ring chromosome 9 in a girl with developmental delay and dysmorphic features: case report and review of the literature. Am J Med Genet A 161A:1447-1452 (2013).
25.
Sigurdardottir S, Goodman BK, Rutberg J, Thomas GH, Jabs EW, et al: Clinical, cytogenetic, and fluorescence in situ hybridization findings in two cases of ‘complete ring' syndrome. Am J Med Genet 87:384-390 (1999).
26.
Sodré CP, Guilherme RS, Meloni VF, Brunoni D, Juliano Y, et al: Ring chromosome instability evaluation in six patients with autosomal rings. Genet Mol Res 9:134-143 (2010).
27.
Sousa SB, Hennekam RC; Nicolaides-Baraitser Syndrome International Consortium: Phenotype and genotype in Nicolaides-Baraitser syndrome. Am J Med Genet C Semin Med Genet 166C:302-314 (2014).
28.
Swinkels ME, Simons A, Smeets DF, Vissers LE, Veltman JA, et al: Clinical and cytogenetic characterization of 13 Dutch patients with deletion 9p syndrome: delineation of the critical region for a consensus phenotype. Am J Med Genet A 146A:1430-1438 (2008).
29.
Van Houdt JK, Nowakowska BA, Sousa SB, van Schaik BD, Seuntjens E, et al: Heterozygous missense mutations in SMARCA2 cause Nicolaides-Baraitser syndrome. Nat Genet 44:445-459 (2012).
30.
Vissers LE, Cox TC, Maga AM, Short KM, Wiradjaja F, et al: Heterozygous mutations of FREM1 are associated with an increased risk of isolated metopic craniosynostosis in humans and mice. PLoS Genet 7:e1002278 (2011).
31.
Wolff D, Endele S, Azzarello-Burri S, Hoyer J, Zweier M, et al: In-frame deletion and missense mutations of the C-terminal helicase domain of SMARCA2 in three patients with Nicolaides-Baraitser syndrome. Mol Syndromol 2:237-244 (2012).
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.