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

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorJEHEE, Fernanda Sarquis
dc.contributor.authorTAKAMORI, Jean Tetsuo
dc.contributor.authorMEDEIROS, Paula F. Vasconcelos
dc.contributor.authorPORDEUS, Ana Carolina B.
dc.contributor.authorLATINI, Flavia Roche M.
dc.contributor.authorBERTOLA, Debora Romeo
dc.contributor.authorKIM, Chong Ae
dc.contributor.authorPASSOS-BUENO, Maria Rita
dc.date.accessioned2017-11-27T16:39:39Z
dc.date.available2017-11-27T16:39:39Z
dc.date.issued2011
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.
dc.description.indexMEDLINE
dc.description.sponsorshipFAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo)
dc.description.sponsorshipCEPID (Centro de Pesquisa, Inovacao e Difusao)
dc.description.sponsorshipCNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico)
dc.identifier.citationEUROPEAN JOURNAL OF MEDICAL GENETICS, v.54, n.4, p.E425-E432, 2011
dc.identifier.doi10.1016/j.ejmg.2011.03.007
dc.identifier.issn1769-7212
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/23802
dc.language.isoeng
dc.publisherELSEVIER SCIENCE BV
dc.relation.ispartofEuropean Journal of Medical Genetics
dc.rightsrestrictedAccess
dc.rights.holderCopyright ELSEVIER SCIENCE BV
dc.subjectMLPA
dc.subjectArray-CGH
dc.subjectCongenital anomalies
dc.subjectMental retardation
dc.subjectSubmicroscopic imbalances
dc.subjectChromosomal abnormalities
dc.subject.otherarray-cgh
dc.subject.othersubtelomeric rearrangements
dc.subject.othergenomic hybridization
dc.subject.otherdysmorphic features
dc.subject.otherabnormalities
dc.subject.otherduplications
dc.subject.othermicroarray
dc.subject.otherdiagnosis
dc.subject.wosGenetics & Heredity
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 countries
dc.typearticle
dc.type.categoryoriginal article
dc.type.versionpublishedVersion
dspace.entity.typePublication
hcfmusp.author.externalJEHEE, Fernanda Sarquis:Univ Sao Paulo, Inst Biociencias, Dept Genet & Biol Evolut, Ctr Estudos Genoma Humano, BR-05508900 Sao Paulo, Brazil
hcfmusp.author.externalMEDEIROS, Paula F. Vasconcelos:Univ Fed Campina Grande, Campina Grande, PB, Brazil
hcfmusp.author.externalPORDEUS, Ana Carolina B.:Univ Fed Campina Grande, Campina Grande, PB, Brazil
hcfmusp.author.externalLATINI, Flavia Roche M.:Univ Fed Sao Paulo, Dept Ginecol, Lab Ginecol Mol, Sao Paulo, Brazil; Assoc Beneficente Coleta Sangue, Sao Paulo, Brazil
hcfmusp.author.externalPASSOS-BUENO, Maria Rita:Univ Sao Paulo, Inst Biociencias, Dept Genet & Biol Evolut, Ctr Estudos Genoma Humano, BR-05508900 Sao Paulo, Brazil
hcfmusp.citation.scopus34
hcfmusp.contributor.author-fmusphcJEAN TETSUO TAKAMORI
hcfmusp.contributor.author-fmusphcDEBORA ROMEO BERTOLA
hcfmusp.contributor.author-fmusphcCHONG AE KIM
hcfmusp.description.beginpageE425
hcfmusp.description.endpageE432
hcfmusp.description.issue4
hcfmusp.description.volume54
hcfmusp.origemWOS
hcfmusp.origem.pubmed21457803
hcfmusp.origem.scopus2-s2.0-79960093690
hcfmusp.origem.wosWOS:000293745000010
hcfmusp.publisher.cityAMSTERDAM
hcfmusp.publisher.countryNETHERLANDS
hcfmusp.relation.referenceRooms L, 2005, HUM MUTAT, V25, P513, DOI 10.1002/humu.20185
hcfmusp.relation.referencede Vries BBA, 2003, J MED GENET, V40, P385, DOI 10.1136/jmg.40.6.385
hcfmusp.relation.referencede Vries BBA, 2001, J MED GENET, V38, P145, DOI 10.1136/jmg.38.3.145
hcfmusp.relation.referenceRauch A, 2006, AM J MED GENET A, V140A, P2063, DOI 10.1002/ajmg.a.31416
hcfmusp.relation.referenceShaffer LG, 2007, AM J MED GENET C, V145C, P335, DOI 10.1002/ajmg.c.30152
hcfmusp.relation.referenceShaw-Smith C, 2004, J MED GENET, V41, P241, DOI 10.1136/jmg.2003.017731
hcfmusp.relation.referenceKirchhoff M, 2007, EUR J MED GENET, V50, P33, DOI 10.1016/j.ejmg.2006.10.002
hcfmusp.relation.referenceRegier DA, 2010, AM J HUM GENET, V86, P765, DOI 10.1016/j.ajhg.2010.03.009
hcfmusp.relation.referenceStegmann APA, 2008, EUR J MED GENET, V51, P93, DOI 10.1016/j.ejmg.2007.10.003
hcfmusp.relation.referenceMiller DT, 2010, AM J HUM GENET, V86, P749, DOI 10.1016/j.ajhg.2010.04.006
hcfmusp.relation.referenceKrepischi-Santos ACV, 2006, CYTOGENET GENOME RES, V115, P254, DOI 10.1159/000095922
hcfmusp.relation.referenceBRUNO DL, 2008, J MED GENET 1117
hcfmusp.relation.referenceGIJSBERS AC, 2009, EUR J HUM GENET 0513
hcfmusp.relation.referenceHOCHSTENBACH R, 2009, EUR J MED GENET 0409
hcfmusp.relation.referenceKriek M, 2007, AM J MED GENET A, V143A, P610, DOI 10.1002/ajmg-a-31593
hcfmusp.scopus.lastupdate2024-05-10
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relation.isAuthorOfPublication.latestForDiscovery10b230f3-e468-44a9-b692-9b7c289ff08a
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