Produção Nacional
Revisado por pares
Extensive CFTR sequencing through NGS in Brazilian individuals with cystic fibrosis: unravelling regional discrepancies in the country
2020; Elsevier BV; Volume: 20; Issue: 3 Linguagem: Inglês
10.1016/j.jcf.2020.08.007
ISSN1873-5010
AutoresLuiz Vicente Ribeiro Ferreira da Silva Filho, Paulo José Cauduro Maróstica, Rodrigo Abensur Athanazio, Francisco J.C. Reis, Neiva Damaceno, Ângela Tavares Paes, Adilson Yuuji Hira, David Schlesinger, Fernando Kok, Margarida D. Amaral, Mara Lícia Machado Antunes, Lilian Cristina Ferreira Andries, Virginia Auxiliadora Freitas de Castro, Fabíola Villac Adde, Maria Fernanda Botelho Hernandez Perez, Vera Maria Dantas, Luciana de Freitas Velloso Monte, Adriana Goya, Samia Zahi Rached, Lusmaia Damaceno Camargo Costa, Lorenna Junqueira Almeida Prado, Elizabet Vilar Guimarães, Ana Cristina de Carvalho Fernández Fonseca, Marina Pires Nishi, Carlos Antônio Riedi, Nelson Augusto Rosário Filho, Mariane Gonçalves Martynychen Canan, Maria Inez Machado Fernandes, Albin Eugênio Augustin, Rosângela Villela Garcia, Maria Margarete da Silva Zembrzuski, Kátia Izabel de Oliveira, Anneliese Hoffmann, Cláudio Ricachinevsky, Paulo de Tarso Roth Dalcin, Bruna Ziegler, Daniela de Souza Paiva Borgli, Daniele Menezes Torres Ferrao, Elizabeth Passos Simoes da Silva, Marı́a Angélica Santana, Maria Amenaide Carvalho Alves de Sousa, Claudia de Castro e Silva, Evalto Monte de Araujo Filho, Tiago Neves Veras, N Ludwig Neto, Luiz Roberto Ágea Cutolo, A Vergara, Suzana Fonseca Oliveira Melo, Maria do Espírito Santo Almeida Moreira, Roberta de Cássia Nunes Cruz Melotti, Fernanda Barbosa dos Santos Malini, Marcelo Bicalho de Fuccio, Bruno Porto Pessoa, Concetta Esposito, Paulo Kussek, Glaunir Maria Foletto, Leonardo Araújo Pinto, Matias Epifânio, Marcelo Tadday Rodrigues, Marta Cristina Teixeira Duarte, Daniela Góis Meneses, Valéria de Carvalho Martins, Sônia Elenita Lopes Valente, Arlan de Azevedo Ferreira, Constantino Giovanni Braga Cartaxo, Denise Maria Costa Haidar, Mônica de Cássia Firmida, Marcos César Santos de Castro, Edna Lúcia Souza, Laís Ribeiro Mota, Katharina Vidal de Negreiros Moura, Joaquim Carlos Rodrigues, Clóvis R. Nakaie, Tânia Wrobel Folescu, Izabela Rocha Sad, Murilo Carlos Amorim de Britto, Carlos Henrique Medeiros Castelletti, Cláudia Mello Gonçalves, Lúcia Harumi Muramatu, Gilberto Bueno Fischer, Giesela Fleischer Ferrari, Luciana Oliveira Silvano Tostes, Carmen Sílvia Bertuzzo, Fernando Augusto Lima Marson, Sônia Mayumi Chiba, Marcela Duarte de Sillos,
Tópico(s)Genomics and Rare Diseases
ResumoBackground The Brazilian population has a tri-hybrid composition with a high degree of ethnic admixture. We hypothesized that Brazilian individuals with CF from different Brazilian regions have a specific distribution of CFTR variants. Methods Individuals with CF with data available in the Patient Registry and without an established genotype were submitted to CFTR sequencing by Next Generation Sequencing (NGS) methodology, and results were anonymously incorporated to the Registry Database. Genotyping results were expressed as 'positive', 'inconclusive' or 'negative'. Logistic regression models were performed to investigate the association between demographic/clinical variables and genotyping results. Mediation analysis was conducted to estimate direct and indirect effects of Brazilian region on a binary positive genotyping response. Results In October 2017, data from 4,654 individuals with CF were available, and 3,104(66.7%) of them had a genotyping result. A total of 236 variants (114 new variants) were identified, with F508del identified in 46% of the alleles tested. Genotyping revealed 2,002(64.5%) individuals positive, 757(24.4%) inconclusive and 345(11.1%) negative. Distribution of genotype categories was markedly different across Brazilian Regions, with greater proportions of negative individuals in the North (45%) and Northeast (26%) regions. Newborn screening (CF-NBS) and age at diagnosis were identified as mediators of the effect of Brazilian region on a positive genotyping result. Conclusions This large initiative of CFTR genotyping showed significant regional discrepancies in Brazil, probably related to socio-economic conditions, lack of adequate CF-NBS and poor access to reliable sweat testing. These results may be useful to indicate Regions where CF care demands more attention.
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