دورية أكاديمية
Extensive CFTR sequencing through NGS in Brazilian individuals with cystic fibrosis: unravelling regional discrepancies in the country.
| العنوان: | Extensive CFTR sequencing through NGS in Brazilian individuals with cystic fibrosis: unravelling regional discrepancies in the country. |
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| المؤلفون: | da Silva Filho LVRF; Pediatric Pulmonology Unit, Instituto da Criança do Hospital das Clínicas da FMUSP, São Paulo, São Paulo, Brazil; Instituto de Ensino e Pesquisa, Hospital Israelita Albert Einstein, São Paulo, SP, Brazil. Electronic address: luizvic@me.com., Maróstica PJC; Pediatric Pulmonology Department, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil., Athanazio RA; Pulmonary Division - Heart Institute (InCor) - Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil., Reis FJC; Pediatric Pulmonology Department, Hospital Infantil João Paulo II - Rede FHEMIG, Belo Horizonte, Minas Gerais, Brazil., Damaceno N; Pediatric Pumonology Department, Santa Casa de São Paulo, São Paulo, São Paulo, Brazil., Paes AT; Faculdade Israelita de Ciências da Saúde Albert Einstein (FICSAE), São Paulo, São Paulo, Brazil., Hira AY; Laboratório de Sistemas Integráveis (LSI), Escola Politécnica da USP, São Paulo, São Paulo, Brazil., Schlesinger D; Mendelics, São Paulo, São Paulo, Brazil., Kok F; Mendelics, São Paulo, São Paulo, Brazil., Amaral MD; BioISI - Biosystems & Integrative Sciences Institute, Lisboa, Faculty of Sciences, University of Lisboa, Portugal. |
| مؤلفون مشاركون: | Brazilian Cystic Fibrosis Patient Registry Contributors Team |
| المصدر: | Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society [J Cyst Fibros] 2021 May; Vol. 20 (3), pp. 473-484. Date of Electronic Publication: 2020 Aug 18. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 101128966 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-5010 (Electronic) Linking ISSN: 15691993 NLM ISO Abbreviation: J Cyst Fibros Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Amsterdam ; New York : Elsevier, c2002- |
| مواضيع طبية MeSH: | Cystic Fibrosis/*genetics , Cystic Fibrosis Transmembrane Conductance Regulator/*genetics, Brazil/epidemiology ; Child ; Child, Preschool ; Cystic Fibrosis/epidemiology ; Female ; Genetic Variation ; Genotype ; Humans ; Infant ; Male ; Registries |
| مستخلص: | Background: 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. Competing Interests: Declaration of Competing Interests Dr. Silva Filho reports grants and personal fees from Vertex Pharmaceuticals, grants from TimPel and Diagnostics of Americas (DASA), personal fees from Roche do Brasil, Boehringer Ingelheim, Glenmark do Brasil, AbbVie, and Sanofi, outside the submitted work. Dr. Marostica reports personal fees from Vertex Pharmaceuticals, grants from Roche, outside the submitted work. Dr. Athanazio reports grants and personal fees from Vertex Pharmaceuticals and Roche do Brasil, grant from GSK, personal fees from Pfizer, Astrazeneca, Chiesi, Novartis, and Boehringer Ingelheim, outside the submitted work. Dr. Reis has no conflicts of interest to declare. Dr. Damaceno reports personal fees from Vertex Pharmaceuticals and Roche do Brasil, outside the submitted work. Dr. Paes and Dr. Hira report personal fees from The Brazilian CF Study Group, during the conduct of the study. Dr. Schlesinger and Dr. Kok report grants from Vertex Pharmaceuticals, during the conduct of the study. Dr. Amaral reports grants and personal fees from Vertex Pharmaceuticals, PTC Pharmaceuticals, and Gilead Sciences Inc., grants from Gilead Génese Programme, Proteostasis Therapeutics, outside the submitted work. Work in MDA lab is supported by UIDB/04046/2020 and UIDP/04046/2020 centre grants (to BioISI) and research grants (to MDA): "iDrugCF" (FCT/02/SAICT/2017/28800) from from FCT/MCTES Portugal; "HIT-CF" (H2020-SC1-2017-755021) from EU; SRC 013 from CF Trust-UK; and "PTSense" (AMARAL19G0) from CFF-USA. (Copyright © 2020. Published by Elsevier B.V.) |
| فهرسة مساهمة: | Investigator: MLM Antunes, Ambulatório Amélio Marques - Universidade Federal de Uberlândia HCU/FAEPU, Uberlândia, Minas Gerais. Electronic address: maraliciamachado@hotmail.com.; LCF Andries, Ambulatório Multidisciplinar de Fibrose Cistica APAE - Iped, Campo Grande, Mato Grosso do Sul. Electronic address: liliandries@yahoo.com.br.; VAF de Castro, APAE Anápolis, Anápolis, Goiás. Electronic address: castrovirginiaa@yahoo.com.br.; FV Adde, Consultorio Fabiola Vilac Adde, São Paulo, São Paulo. Electronic address: fabiola.adde@outlook.com.; MFBH Perez, Centro de Referência de Fibrose Cística do ABC, São Paulo, São Paulo. Electronic address: dra.mariafernanda@outlook.com.br.; VM Dantas, Centro de Referencia em Fibrose Cistica do Rio Grande do Norte, Natal, Rio Grande do Norte. Electronic address: veramdantas@gmail.com.; LFV Monte, Hospital da Criança de Brasilia Jose de Alencar, Brasília, Distrito Federal. Electronic address: luciana_fvm@yahoo.com.br.; A Goya, Hospital da Criança de Brasilia Jose de Alencar, Brasília, Distrito Federal. Electronic address: agoya@uol.com.br.; S Rached, Pulmonary Division - Heart Institute (InCor) - Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil, São Paulo, São Paulo. Electronic address: samia.rached@gmail.com.; LDC Costa, Hospital das Clinicas da Universidade Federal de Goiás, Goiânia, Goiás. Electronic address: lusmaiapneumoped@gmail.com.; LJA Prado, Hospital das Clinicas da Universidade Federal de Goiás - Adult Centre, Goiânia, Goiás. Electronic address: lorennajap@gmail.com.; EV Guimarães, Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais. Electronic address: betvilar@gmail.com.; AC de Carvalho Fernandez Fonseca, Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais. Electronic address: anafernandezfonseca@gmail.com.; MP Nishi, Hospital das Clinicas da Universidade Federal de Minas Gerais - Adult Centre, Belo Horizonte, Minas Gerais. Electronic address: marinanishi@yahoo.com.br.; CA Riedi, Hospital das Clinicas da Universidade Federal do Paraná, Curitiba, Paraná. Electronic address: pneumoriedi@yahoo.com.br.; NAR Filho, Hospital das Clinicas da Universidade Federal do Paraná, Curitiba, Paraná. Electronic address: nelson.rosario@UniversidadeFederaldoParana.br.; MGM Canan, Hospital das Clinicas da Universidade Federal do Paraná - Adult Centre, Curitiba, Paraná. Electronic address: marianegm@hotmail.com.; MIM Fernandes, Hospital das Clinicas da USP Ribeirao Preto, Ribeirão Preto, São Paulo. Electronic address: mimferna@fmrp.usp.br.; AE Augustin, Hospital das Clinicas da USP Ribeirao Preto, Ribeirão Preto, São Paulo. Electronic address: albinaugustin@hotmail.com.; RV Garcia, Hospital das Clinicas da USP Ribeirao Preto - Adult Centre, Ribeirão Preto, São Paulo. Electronic address: rosangelavillela@yahoo.com.br.; MM da Silva Zembrzuski, Hospital de Base do Distrito Federal, Brasília, Distrito Federal. Electronic address: margarete.zem@gmail.com.; KI de Oliveira, Hospital de Base da Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto, São Paulo. Electronic address: kioliveira@unimedriopreto.com.br.; A Hoffmann, Hospital de Clinicas de Porto Alegre, Porto Alegre, Rio Grande do Sul. Electronic address: anneliese.hoffmann@gmail.com.; C Ricachinevsky, Hospital de Clinicas de Porto Alegre, Porto Alegre, Rio Grande do Sul. Electronic address: ricachinevsky@terra.com.br.; P de Tarso Roth Dalcin, Hospital de Clinicas de Porto Alegre - Adult Centre, Porto Alegre, Rio Grande do Sul. Electronic address: pdalcin@terra.com.br.; B Ziegler, Hospital de Clinicas de Porto Alegre - Adult Centre, Porto Alegre, Rio Grande do Sul. Electronic address: brunaziegler@yahoo.com.br.; D de Souza Paiva Borgli, Hospital dos Servidores do Estado Rio de Janeiro, Rio de Janeiro, Rio de Janeiro. Electronic address: daniborgli@gmail.com.; DMT Ferrao, Hospital Dório Silva - SESA, Vitória, Espírito Santo. Electronic address: danimetor@yahoo.com.br.; EPS da Silva, Hospital Dório Silva - SESA, Vitória, Espírito Santo. Electronic address: epassos_silva@yahoo.com.br.; MA Santana, Hospital Especializado Otavio Mangabeira, Salvador, Bahia. Electronic address: mangelicapsantana@gmail.com.; MACA de Sousa, Hospital Especializado Otavio Mangabeira, Salvador, Bahia. Electronic address: amenaidecarvalho@gmail.com.; C de Castro E Silva, Hospital Infantil Albert Sabin, Fortaleza, Ceará. Electronic address: claudiadecsilva@hotmail.com.; EMA Filho, Hospital Infantil Albert Sabin, Fortaleza, Ceará. Electronic address: evalto@gmail.com.; TN Veras, Hospital Infantil Jeser Amarante Faria, Joinvile, Santa Catarina. Electronic address: tnveras@hotmail.com.; NL Neto, Hospital Infantil Joana de Gusmao, Florianópolis, Santa Catarina. Electronic address: norbertoludwig@gmail.com.; LRA Cutolo, Hospital Infantil Joana de Gusmao, Florianópolis, Santa Catarina. Electronic address: lu.cutolo@gmail.com.; AA Vergara, Hospital Infantil João Paulo II/FHEMIG, Belo Horizonte, Minas Gerais. Electronic address: albertovergara1967@gmail.com.; SFO Melo, Hospital Infantil João Paulo II/FHEMIG, Belo Horizonte, Minas Gerais. Electronic address: sfmelo@hotmail.com.; MDESA Moreira, Hospital Infantil Lucídio Portella, Teresina, Piauí. Electronic address: me.santo@uol.com.br.; RCNC Melotti, Hospital Infantil N Sra da Gloria, Vitória, Espírito Santo. Electronic address: roberta.melotti@hotmail.com.; FBDS Malini, Hospital Infantil N Sra da Gloria, Vitória, Espírito Santo. Electronic address: fernandamalini@yahoo.com.br.; MB de Fuccio, Hospital Julia Kubitschek/FHEMIG, Belo Horizonte, Minas Gerais. Electronic address: marcelobf@yahoo.com.br.; BP Pessoa, Hospital Julia Kubitschek/FHEMIG, Belo Horizonte, Minas Gerais. Electronic address: pessoabh2@yahoo.com.br.; C Esposito, Hospital Nereu Ramos, Florianópolis, Santa Catarina. Electronic address: concetta@riabilittare.com.br.; PC Kussek, Hospital Pequeno Principe, Curitiba, Paraná. Electronic address: paulokussek@gmail.com.; GM Foletto, Hospital Santa Isabel, Blumenau, Santa Catarina. Electronic address: glaunirfoletto@hotmail.com.; LA Pinto, Hospital São Lucas - PUCRS, Porto Alegre, Rio Grande do Sul. Electronic address: leonardo.pinto@pucrs.br.; M Epifanio, Hospital São Lucas - PUCRS, Porto Alegre, Rio Grande do Sul. Electronic address: mepifanio@hotmail.com.; MT Rodrigues, Hospital São Lucas - PUCRS - Adult Centre, Porto Alegre, Rio Grande do Sul. Electronic address: marcelo.tadday@gmail.com.; MC Duarte, Hospital Universitario da Universidade Federal de Juiz de Fora, Juiz de Fora, Minas Gerais. Electronic address: martaduarte200@gmail.com.; DG Meneses, Hospital Universitario da Univ Federal de Sergipe, Aracaju, Sergipe. Electronic address: danielagoismeneses@gmail.com.; V de Carvalho Martins, Hospital Universitário João de Barros Barreto, Belém, Pará. Electronic address: vcmartins@hotmail.com.; SEL Valente, Hospital Universitário João de Barros Barreto, Belém, Pará. Electronic address: soniaelenita.sv@gmail.com.; A de Azevedo Ferreira, Hospital Universitário Julio Muller, Cuiabá, Mato Grosso. Electronic address: arlan.fer@gmail.com.; CGB Cartaxo, Hospital Universitario Lauro Wanderley, João Pessoa, Paraíba. Electronic address: constancartaxo@gmail.com.; DMC Haidar, Hospital Universitário Materno-Infantil de São Luis, São Luis, Maranhão. Electronic address: denise.ch@terra.com.br.; MC Firmida, Hospital Universitario Pedro Ernesto - Universidade Estadual do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro. Electronic address: mfirmida@gmail.com.; MCS de Castro, Hospital Universitario Pedro Ernesto - Universidade Estadual do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro. Electronic address: marcoscesaruerj@gmail.com.; ELS de Souza, Hospital Universitario Prof. Edgard Santos - Universidade Federal da Bahia, Salvador, Bahia. Electronic address: souza.ednalucia@gmail.com.; LR Mota, Hospital Universitario Prof. Edgard Santos - Universidade Federal da Bahia, Salvador, Bahia. Electronic address: lais_rmota@hotmail.com.; KV de Negreiros Moura, Hospital Universitario Professor Alberto Antunes, Maceió, Alagoas. Electronic address: kmoura@bol.com.br.; JC Rodrigues, Instituto da Criança, Hospital das Clínicas da FMUSP, São Paulo, São Paulo. Electronic address: qjocarod@uol.com.br.; CMA Nakaie, Instituto da Criança, Hospital das Clínicas da FMUSP, São Paulo, São Paulo. Electronic address: cleydemyriam@gmail.com.; TW Folescu, Instituto Fernandes Figueira, Rio de Janeiro, Rio de Janeiro. Electronic address: tania.folescu@gmail.com.; I Sad, Instituto Fernandes Figueira, Rio de Janeiro, Rio de Janeiro. Electronic address: izabelasad@gmail.com.; MCA de Britto, Instituto de Medicina Integral Prof Fernando Figueira (IMIP), Recife, Pernambuco. Electronic address: murilodebritto@gmail.com.; CHM Castelletti, Laboratório de Imunopatologia Keizo Asami, Universidade Federal de Pernambuco, Recife, Pernambuco. Electronic address: hcastelletti@prospecmol.org.; CM Gonçalves, PAM Codajás, Manaus, Amazônia. Electronic address: cmgr.mao@gmail.com.; L Muramatu, Faculdade de Ciências Médicas da Santa Casa de São Paulo, São Paulo, São Paulo. Electronic address: luciamuramatu@uol.com.br.; GB Fischer, Hospital da Criança Santo Antonio, Porto Alegre, Rio Grande do Sul. Electronic address: gbfinter@gmail.com.; GF Ferrari, UNESP, Botucatu, São Paulo. Electronic address: gferrari@fmb.unesp.br.; LOS Tostes, UNESP, Botucatu, São Paulo. Electronic address: lusilvanomed@gmail.com.; CS Bertuzzo, Universidade Estadual de Campinas - UNICAMP, Campinas, São Paulo. Electronic address: bertuzzo@unicamp.br.; FAL Marson, Universidade Estadual de Campinas - UNICAMP, Campinas, São Paulo. Electronic address: fernandolimamarson@hotmail.com.; SM Chiba, Escola Paulista de Medicina - Universidade Federal de São Paulo - UNIFESP, São Paulo, São Paulo. Electronic address: smchiba@uol.com.br.; MD De Sillos, Escola Paulista de Medicina - Universidade Federal de São Paulo - UNIFESP, São Paulo, São Paulo. Electronic address: marcela.sillos@unifesp.br. Keywords: Brazil; Diagnosis; Genetics; Newborn screening; Sweat chloride |
| المشرفين على المادة: | 126880-72-6 (Cystic Fibrosis Transmembrane Conductance Regulator) |
| تواريخ الأحداث: | Date Created: 20200822 Date Completed: 20220126 Latest Revision: 20220126 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1016/j.jcf.2020.08.007 |
| PMID: | 32819855 |
| قاعدة البيانات: | MEDLINE |
Full Text via ClinicalKey 
Full Text Finder | تدمد: | 1873-5010 |
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| DOI: | 10.1016/j.jcf.2020.08.007 |