HUMAN RING CHROMOSOMES – NEW INSIGHTS FOR THEIR CLINICAL SIGNIFICANCE
Guilherme RS1,2, Klein E1, Hamid AB1, Bhatt S1, Volleth M3, Polityko A4, Kulpanovich A5, Dufke A6, Albrecht B7, Morlot S8, Brecevic L9, Petersen MB10, Manolakos E10, Kosyakova N1, Liehr T1*
*Corresponding Author: Thomas Liehr, Institut für Humangenetik, Kollegiengasse 10, Postfach D-07740 Jena, Germany; Tel.: +49-3641-935533; Fax: +49-3641-935582; E-mail: i8lith@mti.uni-jena.de
page: 13

RESULTS AND DISCUSSION

In 29 cases with ring chromosomes, the chromosomal origin and content could be determined using molecular cytogenetics. The rings were derived from chromosome 4 (one case), 10 (one case), 13 (five cases), 14, (three cases), 18 (two cases), 21 (eight cases), 22 (three cases), X (five cases) and Y (one case). The exact breakpoints and mosaic states are summarized in Table 1 and examples of the FISH results are shown in Figure 1. In the following data, the obtained results were compared with the literature by chromosomal origin; afterwards, the chromosomal imbalances were analyzed, and finally, a conclusion was drawn. Analyzed Rings by Chromosomal Origin. Numerous cases for ring chromosomes 4 have been reported previously [12-14]. Interestingly, those cases fall into two cytogenetic groups: one group where the ring is stable and the other group where it is unstable within the studied cells, as in case R-1. Further studies are necessary to rule out where this instability comes from, and what the clinical impact is. To the best of our knowledge, no clinically normal ring chromosome 4 case has yet been reported. In case R-2, the first ever seen balanced ring formation involving chromosome 10 formed by the Mc- Clintock mechanism [2] is reported. The rearrangement was connected with clinical problems, as the ring was lost in ~20.0% of the cells. Ring chromosomes derived from chromosome 10 are rare (only about 10 cases) and were recently reviewed [15]. Martin et al. [16] suggested the existence of a ring chromosome 13 syndrome and gave an incidence of 1/58,000 in live births. Here, five cases with ring chromosomes 13 were studied (R-3 to R7), all of them were clinically abnormal. Similarly to chromosome 13 derived rings, chromosome 14 is also suggested as a specific syndrome [17]. In concordance with the literature, all three ring chromosome 14 cases studied here (R-8 to R10) had an abnormal pheno-type. Ring chromosomes 18 were present in the prenatally studied cases R-11 and R-12. Here too, a recognizable syndrome was suggested [18]. Similar to chromosome 4, for rings derived from chromosome 18, cytogenetically stable (e.g., present two cases) and unstable rings [19] are reported. Eight cases with ring chromosomes 21 were char-acterized in the present study (cases R-13 to R-20). While cases R-13 to R-15 were unbalanced and led to clinical signs, two of the cases just detected were due to infertility (R-17 and R-20). As reported in [20], most, if not all ring chromosome 21 cases are mosaic, as the ones here described. A ring chromosome 21 syndrome was also postulated [21]. The three ring chromosome 22 cases were either cyto-genetically stable (R-21 and R-22) or unstable (R-23). The reason for the cytogenetic study was available only for case R-21; it was infertility, and in the literature there are several similar cases reported [22]. Turner syndrome is cytogenetically characterized by karyotype 45,X; in ~5.0% of the cases, this main cell line is accompanied by a second one having 46 chromosomes due to an additional derivative X- or Y-chromosome [23]. Here, six such cases were characterized in more detail, as they had a ring derived from the X-chromosome (cases R-24 to R-28) or the Y-chromosome (R-29). Interestingly, all cases were detected during adulthood and only two of them due to a suspicion of Turner syndrome (R-24 and R-26). The majority of the cases were referred due to infertility. Ring Chromosome-Induced Imbalances. In all 29 studied ring chromosome cases (Table 1), euchromatic imbalances were present except for cases R-7, R-21 and R-22. In the latter, clinical data was available only for case R-21, and infertility was the only clinical problem observed there. Primarily, case R-2 did not have any imbalance due to a ring chromosome, but double ring formation and loss of the ring chromosome led to a partial tri - or monosomy in 23.0% of the patient’s cells overall. Imbalances were exclusively induced by the ring chromosome formation in case R-10. Moreover, in all the remaining 24 cases, imbalances were also caused by sec-ondary effects of the ring chromosome formation: i) double ring formation: R-1, R-3 to R-5, R-8, R-15, R-16, R-18 to R-20, R-23, R-28 and R-29; ii) ring doubling: R-1, R-15, R-26 and R-28; iii) complex changes of the ring itself: R-1, R-15 to R-17 and R-23; iv) ring opening (including further rearrangements): R-1, R-8, R-11, R-13, R-15, R-17, R-19, R-20 and R-23; v) loss of the ring: R-1, R-4, R-6, R-8, R-9, R-12 to R-16, R-19 and R-24 to R-29. Similar observations were also made for other ring chromosomes 22. The idea that there might even be a “ring syndrome” irrespective of the chromosomal origin of the ring [24] might be due to the gross imbalances induced by these secondary changes [25].



Number 26
Number 26 VOL. 26(2), 2023 All in one
Number 26
VOL. 26(2), 2023
Number 26
VOL. 26, 2023 Supplement
Number 26
VOL. 26(1), 2023
Number 25
VOL. 25(2), 2022
Number 25
VOL. 25 (1), 2022
Number 24
VOL. 24(2), 2021
Number 24
VOL. 24(1), 2021
Number 23
VOL. 23(2), 2020
Number 22
VOL. 22(2), 2019
Number 22
VOL. 22(1), 2019
Number 22
VOL. 22, 2019 Supplement
Number 21
VOL. 21(2), 2018
Number 21
VOL. 21 (1), 2018
Number 21
VOL. 21, 2018 Supplement
Number 20
VOL. 20 (2), 2017
Number 20
VOL. 20 (1), 2017
Number 19
VOL. 19 (2), 2016
Number 19
VOL. 19 (1), 2016
Number 18
VOL. 18 (2), 2015
Number 18
VOL. 18 (1), 2015
Number 17
VOL. 17 (2), 2014
Number 17
VOL. 17 (1), 2014
Number 16
VOL. 16 (2), 2013
Number 16
VOL. 16 (1), 2013
Number 15
VOL. 15 (2), 2012
Number 15
VOL. 15, 2012 Supplement
Number 15
Vol. 15 (1), 2012
Number 14
14 - Vol. 14 (2), 2011
Number 14
The 9th Balkan Congress of Medical Genetics
Number 14
14 - Vol. 14 (1), 2011
Number 13
Vol. 13 (2), 2010
Number 13
Vol.13 (1), 2010
Number 12
Vol.12 (2), 2009
Number 12
Vol.12 (1), 2009
Number 11
Vol.11 (2),2008
Number 11
Vol.11 (1),2008
Number 10
Vol.10 (2), 2007
Number 10
10 (1),2007
Number 9
1&2, 2006
Number 9
3&4, 2006
Number 8
1&2, 2005
Number 8
3&4, 2004
Number 7
1&2, 2004
Number 6
3&4, 2003
Number 6
1&2, 2003
Number 5
3&4, 2002
Number 5
1&2, 2002
Number 4
Vol.3 (4), 2000
Number 4
Vol.2 (4), 1999
Number 4
Vol.1 (4), 1998
Number 4
3&4, 2001
Number 4
1&2, 2001
Number 3
Vol.3 (3), 2000
Number 3
Vol.2 (3), 1999
Number 3
Vol.1 (3), 1998
Number 2
Vol.3(2), 2000
Number 2
Vol.1 (2), 1998
Number 2
Vol.2 (2), 1999
Number 1
Vol.3 (1), 2000
Number 1
Vol.2 (1), 1999
Number 1
Vol.1 (1), 1998

 

 


 About the journal ::: Editorial ::: Subscription ::: Information for authors ::: Contact
 Copyright © Balkan Journal of Medical Genetics 2006