Mechanisms of ring chromosome formation, ring instability and clinical consequences
Autor(a) principal: | |
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Data de Publicação: | 2011 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://repositorio.unifesp.br/handle/11600/34333 http://dx.doi.org/10.1186/1471-2350-12-171 |
Resumo: | Background: the breakpoints and mechanisms of ring chromosome formation were studied and mapped in 14 patients.Methods: Several techniques were performed such as genome-wide array, MLPA (Multiplex Ligation-Dependent Probe Amplification) and FISH (Fluorescent in situ Hybridization).Results: 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).Conclusions: 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). |
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Guilherme, Roberta dos Santos [UNIFESP]Meloni, Vera de Freitas Ayres [UNIFESP]Kim, Chong A.Pellegrino, Renata [UNIFESP]Takeno, Sylvia Satomi [UNIFESP]Spinner, Nancy B.Conlin, Laura K.Christofolini, Denise Maria [UNIFESP]Kulikowski, Leslie D.Melaragno, Maria Isabel [UNIFESP]Universidade Federal de São Paulo (UNIFESP)Universidade de São Paulo (USP)Childrens Hosp PhiladelphiaSch Med ABC2016-01-24T14:17:34Z2016-01-24T14:17:34Z2011-12-21Bmc Medical Genetics. London: Biomed Central Ltd, v. 12, 7 p., 2011.1471-2350http://repositorio.unifesp.br/handle/11600/34333http://dx.doi.org/10.1186/1471-2350-12-171WOS000301935200001.pdf10.1186/1471-2350-12-171WOS:000301935200001Background: the breakpoints and mechanisms of ring chromosome formation were studied and mapped in 14 patients.Methods: Several techniques were performed such as genome-wide array, MLPA (Multiplex Ligation-Dependent Probe Amplification) and FISH (Fluorescent in situ Hybridization).Results: 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).Conclusions: 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).Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Div Genet, Dept Morphol & Genet, BR-04023900 Botucatu, SP, BrazilUniv São Paulo, Genet Unit, Inst Crianca, BR-05403000 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychobiol, BR-04023900 São Paulo, BrazilChildrens Hosp Philadelphia, Div Genet & Mol Biol, Philadelphia, PA USASch Med ABC, Gynecol & Obstet Div, BR-09060650 São Paulo, BrazilUniv São Paulo, Dept Pathol, BR-05403000 São Paulo, BrazilUniversidade Federal de São Paulo, Div Genet, Dept Morphol & Genet, BR-04023900 Botucatu, SP, BrazilUniversidade Federal de São Paulo, Dept Psychobiol, BR-04023900 São Paulo, BrazilFAPESP: 07/58735-5Web of Science7engBiomed Central LtdBmc Medical GeneticsMechanisms of ring chromosome formation, ring instability and clinical consequencesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPORIGINALWOS000301935200001.pdfapplication/pdf2183662${dspace.ui.url}/bitstream/11600/34333/1/WOS000301935200001.pdf5e9514f3b847c5d80514ce1b292658bfMD51open accessTEXTWOS000301935200001.pdf.txtWOS000301935200001.pdf.txtExtracted texttext/plain31677${dspace.ui.url}/bitstream/11600/34333/2/WOS000301935200001.pdf.txta6306db81f95ef1fa1e70ee05b61fce4MD52open access11600/343332022-07-08 10:33:21.186open accessoai:repositorio.unifesp.br:11600/34333Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652022-07-08T13:33:21Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Mechanisms of ring chromosome formation, ring instability and clinical consequences |
title |
Mechanisms of ring chromosome formation, ring instability and clinical consequences |
spellingShingle |
Mechanisms of ring chromosome formation, ring instability and clinical consequences Guilherme, Roberta dos Santos [UNIFESP] |
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 |
author |
Guilherme, Roberta dos Santos [UNIFESP] |
author_facet |
Guilherme, Roberta dos Santos [UNIFESP] Meloni, Vera de Freitas Ayres [UNIFESP] Kim, Chong A. Pellegrino, Renata [UNIFESP] Takeno, Sylvia Satomi [UNIFESP] Spinner, Nancy B. Conlin, Laura K. Christofolini, Denise Maria [UNIFESP] Kulikowski, Leslie D. Melaragno, Maria Isabel [UNIFESP] |
author_role |
author |
author2 |
Meloni, Vera de Freitas Ayres [UNIFESP] Kim, Chong A. Pellegrino, Renata [UNIFESP] Takeno, Sylvia Satomi [UNIFESP] Spinner, Nancy B. Conlin, Laura K. Christofolini, Denise Maria [UNIFESP] Kulikowski, Leslie D. Melaragno, Maria Isabel [UNIFESP] |
author2_role |
author author author author author author author author author |
dc.contributor.institution.none.fl_str_mv |
Universidade Federal de São Paulo (UNIFESP) Universidade de São Paulo (USP) Childrens Hosp Philadelphia Sch Med ABC |
dc.contributor.author.fl_str_mv |
Guilherme, Roberta dos Santos [UNIFESP] Meloni, Vera de Freitas Ayres [UNIFESP] Kim, Chong A. Pellegrino, Renata [UNIFESP] Takeno, Sylvia Satomi [UNIFESP] Spinner, Nancy B. Conlin, Laura K. Christofolini, Denise Maria [UNIFESP] Kulikowski, Leslie D. Melaragno, Maria Isabel [UNIFESP] |
description |
Background: the breakpoints and mechanisms of ring chromosome formation were studied and mapped in 14 patients.Methods: Several techniques were performed such as genome-wide array, MLPA (Multiplex Ligation-Dependent Probe Amplification) and FISH (Fluorescent in situ Hybridization).Results: 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).Conclusions: 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). |
publishDate |
2011 |
dc.date.issued.fl_str_mv |
2011-12-21 |
dc.date.accessioned.fl_str_mv |
2016-01-24T14:17:34Z |
dc.date.available.fl_str_mv |
2016-01-24T14:17:34Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
Bmc Medical Genetics. London: Biomed Central Ltd, v. 12, 7 p., 2011. |
dc.identifier.uri.fl_str_mv |
http://repositorio.unifesp.br/handle/11600/34333 http://dx.doi.org/10.1186/1471-2350-12-171 |
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1471-2350 |
dc.identifier.file.none.fl_str_mv |
WOS000301935200001.pdf |
dc.identifier.doi.none.fl_str_mv |
10.1186/1471-2350-12-171 |
dc.identifier.wos.none.fl_str_mv |
WOS:000301935200001 |
identifier_str_mv |
Bmc Medical Genetics. London: Biomed Central Ltd, v. 12, 7 p., 2011. 1471-2350 WOS000301935200001.pdf 10.1186/1471-2350-12-171 WOS:000301935200001 |
url |
http://repositorio.unifesp.br/handle/11600/34333 http://dx.doi.org/10.1186/1471-2350-12-171 |
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eng |
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Biomed Central Ltd |
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Biomed Central Ltd |
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