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dc.contributor.authorJehee, Fernanda Sarquis
dc.contributor.authorTakamori, Jean Tetsuo
dc.contributor.authorVasconcelos Medeiros, Paula F.
dc.contributor.authorPordeus, Ana Carolina B.
dc.contributor.authorLatini, Flavia Roche Moreira [UNIFESP]
dc.contributor.authorBertola, Debora Romeo
dc.contributor.authorKim, Chong Ae
dc.contributor.authorPassos-Bueno, Maria Rita
dc.date.accessioned2016-01-24T14:16:54Z
dc.date.available2016-01-24T14:16:54Z
dc.date.issued2011-07-01
dc.identifierhttp://dx.doi.org/10.1016/j.ejmg.2011.03.007
dc.identifier.citationEuropean Journal of Medical Genetics. Amsterdam: Elsevier B.V., v. 54, n. 4, p. E425-E432, 2011.
dc.identifier.issn1769-7212
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/33812
dc.description.abstractConventional 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.en
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipCEPID (Centro de Pesquisa, Inovacao e Difusao)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.format.extentE425-E432
dc.language.isoeng
dc.publisherElsevier B.V.
dc.relation.ispartofEuropean Journal of Medical Genetics
dc.rightsAcesso aberto
dc.subjectMLPAen
dc.subjectArray-CGHen
dc.subjectCongenital anomaliesen
dc.subjectMental retardationen
dc.subjectSubmicroscopic imbalancesen
dc.subjectChromosomal abnormalitiesen
dc.titleUsing a combination of MLPA kits to detect chromosomal imbalances in patients with multiple congenital anomalies and mental retardation is a valuable choice for developing countriesen
dc.typeArtigo
dc.rights.licensehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniv Fed Campina Grande
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionAssoc Beneficente Coleta Sangue
dc.description.affiliationUniv São Paulo, Inst Biociencias, Dept Genet & Biol Evolut, Ctr Estudos Genoma Humano, BR-05508900 São Paulo, Brazil
dc.description.affiliationUniv São Paulo, Fac Med, Dept Oncol, BR-05508 São Paulo, Brazil
dc.description.affiliationUniv Fed Campina Grande, Campina Grande, PB, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Ginecol, Lab Ginecol Mol, São Paulo, Brazil
dc.description.affiliationAssoc Beneficente Coleta Sangue, São Paulo, Brazil
dc.description.affiliationUniv São Paulo, Fac Med, Inst Crianca, BR-05508 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Ginecol, Lab Ginecol Mol, São Paulo, Brazil
dc.identifier.fileWOS000293745000010.pdf
dc.identifier.doi10.1016/j.ejmg.2011.03.007
dc.description.sourceWeb of Science
dc.identifier.wosWOS:000293745000010


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