Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSPDIAS, Alexandre TorchioZANARDO, Evelin AlineDUTRA, Roberta LelisPIAZZON, Flavia BalboNOVO-FILHO, Gil MonteiroMONTENEGRO, Marilia MoreiraNASCIMENTO, Amom MendesROCHA, MarianaMADIA, Fabricia Andreia RosaCOSTA, Thais Virginia Moura MachadoMILANI, CintiaSCHULTZ, ReginaGONCALVES, Fernanda ToledoFRIDMAN, CintiaYAMAMOTO, Guilherme LopesBERTOLA, Debora RomeoKIM, Chong AeKULIKOWSKI, Leslie Domenici2016-10-172016-10-172016EXPERIMENTAL AND MOLECULAR PATHOLOGY, v.101, n.1, p.116-123, 20160014-4800https://observatorio.fm.usp.br/handle/OPI/16214Congenital anomalies are the second highest cause of infant deaths, and, in most cases, diagnosis is a challenge. In this study, we characterize patterns of DNA copy number aberrations in different samples of post-mortem tissues from patients with congenital malformations. Twenty-eight patients undergoing autopsy were cytogenomically evaluated using several methods, specifically, Multiplex Ligation-dependent Probe Amplification (MLPA), micro satellite marker analysis with a MiniFiler kit, FISH, a cytogenomic array technique and bidirectional Sanger sequencing, which were performed on samples of different tissues (brain, heart, liver, skin and diaphragm) preserved in RNAlater, in formaldehyde or by paraffin -embedding. The results identified 13 patients with pathogenic copy number variations (CNVs). Of these, eight presented aneuploidies involving chromosomes 13, 18, 21, X and Y (two presented inter- and intra-tissue mosaicism). In addition, other abnormalities were found, including duplication of the TYMS gene (18p1132); deletion of the CHL1 gene (3p26.3); deletion of the HIC1 gene (17p13.3); and deletion of the TOM1L2 gene (17p11.2). One patient had a pathogenic missense mutation of g.8535C > G (c.746C > G) in exon 7 of the FGFR3 gene consistent with Thanatophoric Dysplasia type I. Cytogenomic techniques were reliable for the analysis of autopsy material and allowed the identification of inter- and intra-tissue mosaicism and a better understanding of the pathogenesis of congenital malformations.engrestrictedAccessCongenital malformationsPost-mortem cytogenomic investigationDNA copy number variationsmissense fgfr3 mutationsmiller-dieker-syndromethymidylate synthasemice deficientgene hic1mosaicismexpressionsequencedeletiondefectsarticleCopyright ACADEMIC PRESS INC ELSEVIER SCIENCE10.1016/j.yexmp.2016.07.003Pathology1096-0945