Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSPJEHEE, Fernanda SarquisTAKAMORI, Jean TetsuoMEDEIROS, Paula F. VasconcelosPORDEUS, Ana Carolina B.LATINI, Flavia Roche M.BERTOLA, Debora RomeoKIM, Chong AePASSOS-BUENO, Maria Rita2017-11-272017-11-272011EUROPEAN JOURNAL OF MEDICAL GENETICS, v.54, n.4, p.E425-E432, 20111769-7212https://observatorio.fm.usp.br/handle/OPI/23802Conventional 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.engrestrictedAccessMLPAArray-CGHCongenital anomaliesMental retardationSubmicroscopic imbalancesChromosomal abnormalitiesarray-cghsubtelomeric rearrangementsgenomic hybridizationdysmorphic featuresabnormalitiesduplicationsmicroarraydiagnosisarticleCopyright ELSEVIER SCIENCE BV10.1016/j.ejmg.2011.03.007Genetics & Heredity