Post-mortem cytogenomic investigations in patients with congenital malformations.
Alexandre Torchio Dias, Évelin Aline Zanardo, Roberta Lelis Dutra, Flavia Balbo Piazzon, Gil Monteiro Novo-Filho, Marilia Moreira Montenegro, Amom Mendes Nascimento, Mariana Rocha, Fabricia Andreia Rosa Madia, Thais Virgínia Moura Machado Costa, Cintia Milani, Regina Schultz, Fernanda Toledo Gonçalves, Cintia Fridman, Guilherme Lopes Yamamoto, Débora Romeo Bertola, Chong Ae Kim, Leslie Domenici Kulikowski
Experimental and molecular pathology 2016 AugCongenital 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), microsatellite 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 (18p11.32); 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. Copyright © 2016 Elsevier Inc. All rights reserved.
Citation
Alexandre Torchio Dias, Évelin Aline Zanardo, Roberta Lelis Dutra, Flavia Balbo Piazzon, Gil Monteiro Novo-Filho, Marilia Moreira Montenegro, Amom Mendes Nascimento, Mariana Rocha, Fabricia Andreia Rosa Madia, Thais Virgínia Moura Machado Costa, Cintia Milani, Regina Schultz, Fernanda Toledo Gonçalves, Cintia Fridman, Guilherme Lopes Yamamoto, Débora Romeo Bertola, Chong Ae Kim, Leslie Domenici Kulikowski. Post-mortem cytogenomic investigations in patients with congenital malformations. Experimental and molecular pathology. 2016 Aug;101(1):116-23
PMID: 27450648
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