Using a combination of MLPA kits to detect chromosomal imbalances in patients with multiple congenital anomalies and mental retardation is a valuable choice for developing countries
Autor(a) principal: | |
---|---|
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/11600/33812 http://dx.doi.org/10.1016/j.ejmg.2011.03.007 |
Resumo: | Conventional karyotyping detects anomalies in 3-15% of patients with multiple congenital anomalies and mental retardation (MCA/MR). Whole-genome array screening (WGAS) has been consistently suggested as the first choice diagnostic test for this group of patients, but it is very costly for large-scale use in developing countries. We evaluated the use of a combination of Multiplex Ligation-dependent Probe Amplification (MLPA) kits to increase the detection rate of chromosomal abnormalities in MCA/MR patients. We screened 261 MCA/MR patients with two subtelomeric and one microdeletion kits. This would theoretically detect up to 70% of all submicroscopic abnormalities. Additionally we scored the de Vries score for 209 patients in an effort to find a suitable cut-off for MLPA screening. Our results reveal that chromosomal abnormalities were present in 87 (33.3%) patients, but only 57 (21.8%) were considered causative. Karyotyping detected 15 abnormalities (6.9%), while MLPA identified 54 (20.7%). Our combined MLPA screening raised the total detection number of pathogenic imbalances more than three times when compared to conventional karyotyping. We also show that using the de Vries score as a cutoff for this screening would only be suitable under financial restrictions. A decision analytic model was constructed with three possible strategies: karyotype, karyotype + MLPA and karyotype + WGAS. Karyotype + MLPA strategy detected anomalies in 19.8% of cases which account for 76.45% of the expected yield for karyotype + WGAS. Incremental Cost Effectiveness Ratio (ICER) of MLPA is three times lower than that of WGAS, which means that, for the same costs, we have three additional diagnoses with MLPA but only one with WGAS. We list all causative alterations found, including rare findings, such as reciprocal duplications of regions deleted in Sotos and Williams-Beuren syndromes. We also describe imbalances that were considered polymorphisms or rare variants, such as the new SNP that confounded the analysis of the 22q13.3 deletion syndrome. (C) 2011 Elsevier Masson SAS. All rights reserved. |
id |
UFSP_c58e07c7e001405d30b8e05c52080407 |
---|---|
oai_identifier_str |
oai:repositorio.unifesp.br:11600/33812 |
network_acronym_str |
UFSP |
network_name_str |
Repositório Institucional da UNIFESP |
repository_id_str |
3465 |
spelling |
Jehee, Fernanda SarquisTakamori, Jean TetsuoVasconcelos Medeiros, Paula F.Pordeus, Ana Carolina B.Latini, Flavia Roche Moreira [UNIFESP]Bertola, Debora RomeoKim, Chong AePassos-Bueno, Maria RitaUniversidade de São Paulo (USP)Univ Fed Campina GrandeUniversidade Federal de São Paulo (UNIFESP)Assoc Beneficente Coleta Sangue2016-01-24T14:16:54Z2016-01-24T14:16:54Z2011-07-01European Journal of Medical Genetics. Amsterdam: Elsevier B.V., v. 54, n. 4, p. E425-E432, 2011.1769-7212http://repositorio.unifesp.br/handle/11600/33812http://dx.doi.org/10.1016/j.ejmg.2011.03.007WOS000293745000010.pdf10.1016/j.ejmg.2011.03.007WOS:000293745000010Conventional karyotyping detects anomalies in 3-15% of patients with multiple congenital anomalies and mental retardation (MCA/MR). Whole-genome array screening (WGAS) has been consistently suggested as the first choice diagnostic test for this group of patients, but it is very costly for large-scale use in developing countries. We evaluated the use of a combination of Multiplex Ligation-dependent Probe Amplification (MLPA) kits to increase the detection rate of chromosomal abnormalities in MCA/MR patients. We screened 261 MCA/MR patients with two subtelomeric and one microdeletion kits. This would theoretically detect up to 70% of all submicroscopic abnormalities. Additionally we scored the de Vries score for 209 patients in an effort to find a suitable cut-off for MLPA screening. Our results reveal that chromosomal abnormalities were present in 87 (33.3%) patients, but only 57 (21.8%) were considered causative. Karyotyping detected 15 abnormalities (6.9%), while MLPA identified 54 (20.7%). Our combined MLPA screening raised the total detection number of pathogenic imbalances more than three times when compared to conventional karyotyping. We also show that using the de Vries score as a cutoff for this screening would only be suitable under financial restrictions. A decision analytic model was constructed with three possible strategies: karyotype, karyotype + MLPA and karyotype + WGAS. Karyotype + MLPA strategy detected anomalies in 19.8% of cases which account for 76.45% of the expected yield for karyotype + WGAS. Incremental Cost Effectiveness Ratio (ICER) of MLPA is three times lower than that of WGAS, which means that, for the same costs, we have three additional diagnoses with MLPA but only one with WGAS. We list all causative alterations found, including rare findings, such as reciprocal duplications of regions deleted in Sotos and Williams-Beuren syndromes. We also describe imbalances that were considered polymorphisms or rare variants, such as the new SNP that confounded the analysis of the 22q13.3 deletion syndrome. (C) 2011 Elsevier Masson SAS. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)CEPID (Centro de Pesquisa, Inovacao e Difusao)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Univ São Paulo, Inst Biociencias, Dept Genet & Biol Evolut, Ctr Estudos Genoma Humano, BR-05508900 São Paulo, BrazilUniv São Paulo, Fac Med, Dept Oncol, BR-05508 São Paulo, BrazilUniv Fed Campina Grande, Campina Grande, PB, BrazilUniversidade Federal de São Paulo, Dept Ginecol, Lab Ginecol Mol, São Paulo, BrazilAssoc Beneficente Coleta Sangue, São Paulo, BrazilUniv São Paulo, Fac Med, Inst Crianca, BR-05508 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Ginecol, Lab Ginecol Mol, São Paulo, BrazilWeb of ScienceE425-E432engElsevier B.V.European Journal of Medical Geneticshttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policyinfo:eu-repo/semantics/openAccessMLPAArray-CGHCongenital anomaliesMental retardationSubmicroscopic imbalancesChromosomal abnormalitiesUsing a combination of MLPA kits to detect chromosomal imbalances in patients with multiple congenital anomalies and mental retardation is a valuable choice for developing countriesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlereponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPORIGINALWOS000293745000010.pdfapplication/pdf612759${dspace.ui.url}/bitstream/11600/33812/1/WOS000293745000010.pdf5c03f1a066fa8aa8b2ee0898c1532823MD51open accessTEXTWOS000293745000010.pdf.txtWOS000293745000010.pdf.txtExtracted texttext/plain40888${dspace.ui.url}/bitstream/11600/33812/2/WOS000293745000010.pdf.txt53910b16377419e90b3b95c0eecd23efMD52open access11600/338122022-02-18 10:14:10.228open accessoai:repositorio.unifesp.br:11600/33812Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652022-02-18T13:14:10Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Using a combination of MLPA kits to detect chromosomal imbalances in patients with multiple congenital anomalies and mental retardation is a valuable choice for developing countries |
title |
Using a combination of MLPA kits to detect chromosomal imbalances in patients with multiple congenital anomalies and mental retardation is a valuable choice for developing countries |
spellingShingle |
Using a combination of MLPA kits to detect chromosomal imbalances in patients with multiple congenital anomalies and mental retardation is a valuable choice for developing countries Jehee, Fernanda Sarquis MLPA Array-CGH Congenital anomalies Mental retardation Submicroscopic imbalances Chromosomal abnormalities |
title_short |
Using a combination of MLPA kits to detect chromosomal imbalances in patients with multiple congenital anomalies and mental retardation is a valuable choice for developing countries |
title_full |
Using a combination of MLPA kits to detect chromosomal imbalances in patients with multiple congenital anomalies and mental retardation is a valuable choice for developing countries |
title_fullStr |
Using a combination of MLPA kits to detect chromosomal imbalances in patients with multiple congenital anomalies and mental retardation is a valuable choice for developing countries |
title_full_unstemmed |
Using a combination of MLPA kits to detect chromosomal imbalances in patients with multiple congenital anomalies and mental retardation is a valuable choice for developing countries |
title_sort |
Using a combination of MLPA kits to detect chromosomal imbalances in patients with multiple congenital anomalies and mental retardation is a valuable choice for developing countries |
author |
Jehee, Fernanda Sarquis |
author_facet |
Jehee, Fernanda Sarquis Takamori, Jean Tetsuo Vasconcelos Medeiros, Paula F. Pordeus, Ana Carolina B. Latini, Flavia Roche Moreira [UNIFESP] Bertola, Debora Romeo Kim, Chong Ae Passos-Bueno, Maria Rita |
author_role |
author |
author2 |
Takamori, Jean Tetsuo Vasconcelos Medeiros, Paula F. Pordeus, Ana Carolina B. Latini, Flavia Roche Moreira [UNIFESP] Bertola, Debora Romeo Kim, Chong Ae Passos-Bueno, Maria Rita |
author2_role |
author author author author author author author |
dc.contributor.institution.none.fl_str_mv |
Universidade de São Paulo (USP) Univ Fed Campina Grande Universidade Federal de São Paulo (UNIFESP) Assoc Beneficente Coleta Sangue |
dc.contributor.author.fl_str_mv |
Jehee, Fernanda Sarquis Takamori, Jean Tetsuo Vasconcelos Medeiros, Paula F. Pordeus, Ana Carolina B. Latini, Flavia Roche Moreira [UNIFESP] Bertola, Debora Romeo Kim, Chong Ae Passos-Bueno, Maria Rita |
dc.subject.eng.fl_str_mv |
MLPA Array-CGH Congenital anomalies Mental retardation Submicroscopic imbalances Chromosomal abnormalities |
topic |
MLPA Array-CGH Congenital anomalies Mental retardation Submicroscopic imbalances Chromosomal abnormalities |
description |
Conventional karyotyping detects anomalies in 3-15% of patients with multiple congenital anomalies and mental retardation (MCA/MR). Whole-genome array screening (WGAS) has been consistently suggested as the first choice diagnostic test for this group of patients, but it is very costly for large-scale use in developing countries. We evaluated the use of a combination of Multiplex Ligation-dependent Probe Amplification (MLPA) kits to increase the detection rate of chromosomal abnormalities in MCA/MR patients. We screened 261 MCA/MR patients with two subtelomeric and one microdeletion kits. This would theoretically detect up to 70% of all submicroscopic abnormalities. Additionally we scored the de Vries score for 209 patients in an effort to find a suitable cut-off for MLPA screening. Our results reveal that chromosomal abnormalities were present in 87 (33.3%) patients, but only 57 (21.8%) were considered causative. Karyotyping detected 15 abnormalities (6.9%), while MLPA identified 54 (20.7%). Our combined MLPA screening raised the total detection number of pathogenic imbalances more than three times when compared to conventional karyotyping. We also show that using the de Vries score as a cutoff for this screening would only be suitable under financial restrictions. A decision analytic model was constructed with three possible strategies: karyotype, karyotype + MLPA and karyotype + WGAS. Karyotype + MLPA strategy detected anomalies in 19.8% of cases which account for 76.45% of the expected yield for karyotype + WGAS. Incremental Cost Effectiveness Ratio (ICER) of MLPA is three times lower than that of WGAS, which means that, for the same costs, we have three additional diagnoses with MLPA but only one with WGAS. We list all causative alterations found, including rare findings, such as reciprocal duplications of regions deleted in Sotos and Williams-Beuren syndromes. We also describe imbalances that were considered polymorphisms or rare variants, such as the new SNP that confounded the analysis of the 22q13.3 deletion syndrome. (C) 2011 Elsevier Masson SAS. All rights reserved. |
publishDate |
2011 |
dc.date.issued.fl_str_mv |
2011-07-01 |
dc.date.accessioned.fl_str_mv |
2016-01-24T14:16:54Z |
dc.date.available.fl_str_mv |
2016-01-24T14:16:54Z |
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 |
European Journal of Medical Genetics. Amsterdam: Elsevier B.V., v. 54, n. 4, p. E425-E432, 2011. |
dc.identifier.uri.fl_str_mv |
http://repositorio.unifesp.br/handle/11600/33812 http://dx.doi.org/10.1016/j.ejmg.2011.03.007 |
dc.identifier.issn.none.fl_str_mv |
1769-7212 |
dc.identifier.file.none.fl_str_mv |
WOS000293745000010.pdf |
dc.identifier.doi.none.fl_str_mv |
10.1016/j.ejmg.2011.03.007 |
dc.identifier.wos.none.fl_str_mv |
WOS:000293745000010 |
identifier_str_mv |
European Journal of Medical Genetics. Amsterdam: Elsevier B.V., v. 54, n. 4, p. E425-E432, 2011. 1769-7212 WOS000293745000010.pdf 10.1016/j.ejmg.2011.03.007 WOS:000293745000010 |
url |
http://repositorio.unifesp.br/handle/11600/33812 http://dx.doi.org/10.1016/j.ejmg.2011.03.007 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.none.fl_str_mv |
European Journal of Medical Genetics |
dc.rights.driver.fl_str_mv |
http://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
http://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
E425-E432 |
dc.publisher.none.fl_str_mv |
Elsevier B.V. |
publisher.none.fl_str_mv |
Elsevier B.V. |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UNIFESP instname:Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
instname_str |
Universidade Federal de São Paulo (UNIFESP) |
instacron_str |
UNIFESP |
institution |
UNIFESP |
reponame_str |
Repositório Institucional da UNIFESP |
collection |
Repositório Institucional da UNIFESP |
bitstream.url.fl_str_mv |
${dspace.ui.url}/bitstream/11600/33812/1/WOS000293745000010.pdf ${dspace.ui.url}/bitstream/11600/33812/2/WOS000293745000010.pdf.txt |
bitstream.checksum.fl_str_mv |
5c03f1a066fa8aa8b2ee0898c1532823 53910b16377419e90b3b95c0eecd23ef |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 |
repository.name.fl_str_mv |
Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP) |
repository.mail.fl_str_mv |
|
_version_ |
1802764108499517440 |