FLAVIA BALBO PIAZZON
Projetos de Pesquisa
Unidades Organizacionais
LIM/03 - Laboratório de Medicina Laboratorial, Hospital das Clínicas, Faculdade de Medicina
2 resultados
Resultados de Busca
Agora exibindo 1 - 2 de 2
- Subtelomeric Copy Number Variations: The Importance of 4p/4q Deletions in Patients with Congenital Anomalies and Developmental Disability(2016) NOVO-FILHO, Gil M.; MONTENEGRO, Marilia M.; ZANARDO, Evelin A.; DUTRA, Roberta L.; DIAS, Alexandre T.; PIAZZON, Flavia B.; COSTA, Tais V. M. M.; NASCIMENTO, Amom M.; HONJO, Rachel S.; KIM, Chong A.; KULIKOWSKI, Leslie D.The most prevalent structural variations in the human genome are copy number variations (CNVs), which appear predominantly in the subtelomeric regions. Variable sizes of 4p/4q CNVs have been associated with several different psychiatric findings and developmental disability (DD). We analyzed 105 patients with congenital anomalies (CA) and developmental and/or intellectual disabilities (DD/ID) using MLPA subtelomeric specific kits (P036 /P070) and 4 of them using microarrays. We found abnormal subtelomeric CNVs in 15 patients (14.3%), including 8 patients with subtelomeric deletions at 4p/4q (53.3%). Additional genomic changes were observed at 1p36, 2q37.3, 5p15.3, 5q35.3, 8p23.3, 13q11, 14q32.3, 15q11.2, and Xq28/Yq12. This indicates the prevalence of independent deletions at 4p/4q, involving PIGG, TRIML2, and FRG1. Furthermore, we identified 15 genes with changes in copy number that contribute to neurological development and/or function, among them CRMP1, SORCS2, SLC25A4, and HELT. Our results highlight the association of genes with changes in copy number at 4p and 4q subtelomeric regions and the DD phenotype. Cytogenomic characterization of additional cases with distal deletions should help clarifying the role of subtelomeric CNVs in neurological diseases. (C) 2016 S. Karger AG, Basel
- Post-mortem cytogenomic investigations in patients with congenital malformations(2016) DIAS, Alexandre Torchio; ZANARDO, Evelin Aline; DUTRA, Roberta Lelis; PIAZZON, Flavia Balbo; NOVO-FILHO, Gil Monteiro; MONTENEGRO, Marilia Moreira; NASCIMENTO, Amom Mendes; ROCHA, Mariana; MADIA, Fabricia Andreia Rosa; COSTA, Thais Virginia Moura Machado; MILANI, Cintia; SCHULTZ, Regina; GONCALVES, Fernanda Toledo; FRIDMAN, Cintia; YAMAMOTO, Guilherme Lopes; BERTOLA, Debora Romeo; KIM, Chong Ae; KULIKOWSKI, Leslie DomeniciCongenital 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.