Mechanisms of ring chromosome formation, ring instability and clinical consequences

<p>Abstract</p> <p>Background</p> <p>The breakpoints and mechanisms of ring chromosome formation were studied and mapped in 14 patients.</p> <p>Methods</p> <p>Several techniques were performed such as genome-wide array, MLPA (Multiplex Ligation-D...

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Main Authors: Guilherme Roberta S, Ayres Meloni Vera F, Kim Chong A, Pellegrino Renata, Takeno Sylvia S, Spinner Nancy B, Conlin Laura K, Christofolini Denise M, Kulikowski Leslie D, Melaragno Maria I
Format: Article
Language:English
Published: BMC 2011-12-01
Series:BMC Medical Genetics
Online Access:http://www.biomedcentral.com/1471-2350/12/171
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spelling doaj-2cdd4bde58e94dc8a41ac78508ce06552021-04-02T03:42:39ZengBMCBMC Medical Genetics1471-23502011-12-0112117110.1186/1471-2350-12-171Mechanisms of ring chromosome formation, ring instability and clinical consequencesGuilherme Roberta SAyres Meloni Vera FKim Chong APellegrino RenataTakeno Sylvia SSpinner Nancy BConlin Laura KChristofolini Denise MKulikowski Leslie DMelaragno Maria I<p>Abstract</p> <p>Background</p> <p>The breakpoints and mechanisms of ring chromosome formation were studied and mapped in 14 patients.</p> <p>Methods</p> <p>Several techniques were performed such as genome-wide array, MLPA (Multiplex Ligation-Dependent Probe Amplification) and FISH (Fluorescent <it>in situ </it>Hybridization).</p> <p>Results</p> <p>The ring chromosomes of patients I to XIV were determined to be, respectively: r(3)(p26.1q29), r(4)(p16.3q35.2), r(10)(p15.3q26.2), r(10)(p15.3q26.13), r(13)(p13q31.1), r(13)(p13q34), r(14)(p13q32.33), r(15)(p13q26.2), r(18)(p11.32q22.2), r(18)(p11.32q21.33), r(18)(p11.21q23), r(22)(p13q13.33), r(22)(p13q13.2), and r(22)(p13q13.2). These rings were found to have been formed by different mechanisms, such as: breaks in both chromosome arms followed by end-to-end reunion (patients IV, VIII, IX, XI, XIII and XIV); a break in one chromosome arm followed by fusion with the subtelomeric region of the other (patients I and II); a break in one chromosome arm followed by fusion with the opposite telomeric region (patients III and X); fusion of two subtelomeric regions (patient VII); and telomere-telomere fusion (patient XII). Thus, the r(14) and one r(22) can be considered complete rings, since there was no loss of relevant genetic material. Two patients (V and VI) with r(13) showed duplication along with terminal deletion of 13q, one of them proved to be inverted, a mechanism known as inv-dup-del. Ring instability was detected by ring loss and secondary aberrations in all but three patients, who presented stable ring chromosomes (II, XIII and XIV).</p> <p>Conclusions</p> <p>We concluded that the clinical phenotype of patients with ring chromosomes may be related with different factors, including gene haploinsufficiency, gene duplications and ring instability. Epigenetic factors due to the circular architecture of ring chromosomes must also be considered, since even complete ring chromosomes can result in phenotypic alterations, as observed in our patients with complete r(14) and r(22).</p> http://www.biomedcentral.com/1471-2350/12/171
collection DOAJ
language English
format Article
sources DOAJ
author Guilherme Roberta S
Ayres Meloni Vera F
Kim Chong A
Pellegrino Renata
Takeno Sylvia S
Spinner Nancy B
Conlin Laura K
Christofolini Denise M
Kulikowski Leslie D
Melaragno Maria I
spellingShingle Guilherme Roberta S
Ayres Meloni Vera F
Kim Chong A
Pellegrino Renata
Takeno Sylvia S
Spinner Nancy B
Conlin Laura K
Christofolini Denise M
Kulikowski Leslie D
Melaragno Maria I
Mechanisms of ring chromosome formation, ring instability and clinical consequences
BMC Medical Genetics
author_facet Guilherme Roberta S
Ayres Meloni Vera F
Kim Chong A
Pellegrino Renata
Takeno Sylvia S
Spinner Nancy B
Conlin Laura K
Christofolini Denise M
Kulikowski Leslie D
Melaragno Maria I
author_sort Guilherme Roberta S
title Mechanisms of ring chromosome formation, ring instability and clinical consequences
title_short Mechanisms of ring chromosome formation, ring instability and clinical consequences
title_full Mechanisms of ring chromosome formation, ring instability and clinical consequences
title_fullStr Mechanisms of ring chromosome formation, ring instability and clinical consequences
title_full_unstemmed Mechanisms of ring chromosome formation, ring instability and clinical consequences
title_sort mechanisms of ring chromosome formation, ring instability and clinical consequences
publisher BMC
series BMC Medical Genetics
issn 1471-2350
publishDate 2011-12-01
description <p>Abstract</p> <p>Background</p> <p>The breakpoints and mechanisms of ring chromosome formation were studied and mapped in 14 patients.</p> <p>Methods</p> <p>Several techniques were performed such as genome-wide array, MLPA (Multiplex Ligation-Dependent Probe Amplification) and FISH (Fluorescent <it>in situ </it>Hybridization).</p> <p>Results</p> <p>The ring chromosomes of patients I to XIV were determined to be, respectively: r(3)(p26.1q29), r(4)(p16.3q35.2), r(10)(p15.3q26.2), r(10)(p15.3q26.13), r(13)(p13q31.1), r(13)(p13q34), r(14)(p13q32.33), r(15)(p13q26.2), r(18)(p11.32q22.2), r(18)(p11.32q21.33), r(18)(p11.21q23), r(22)(p13q13.33), r(22)(p13q13.2), and r(22)(p13q13.2). These rings were found to have been formed by different mechanisms, such as: breaks in both chromosome arms followed by end-to-end reunion (patients IV, VIII, IX, XI, XIII and XIV); a break in one chromosome arm followed by fusion with the subtelomeric region of the other (patients I and II); a break in one chromosome arm followed by fusion with the opposite telomeric region (patients III and X); fusion of two subtelomeric regions (patient VII); and telomere-telomere fusion (patient XII). Thus, the r(14) and one r(22) can be considered complete rings, since there was no loss of relevant genetic material. Two patients (V and VI) with r(13) showed duplication along with terminal deletion of 13q, one of them proved to be inverted, a mechanism known as inv-dup-del. Ring instability was detected by ring loss and secondary aberrations in all but three patients, who presented stable ring chromosomes (II, XIII and XIV).</p> <p>Conclusions</p> <p>We concluded that the clinical phenotype of patients with ring chromosomes may be related with different factors, including gene haploinsufficiency, gene duplications and ring instability. Epigenetic factors due to the circular architecture of ring chromosomes must also be considered, since even complete ring chromosomes can result in phenotypic alterations, as observed in our patients with complete r(14) and r(22).</p>
url http://www.biomedcentral.com/1471-2350/12/171
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