title: CFTR genotype and clinical outcomes of adult patients carried as cystic fibrosis disease.
abstract: BACKGROUND
  There are nearly 2000 cystic fibrosis transmembrane regulator (CFTR) mutations that cause cystic fibrosis (CF). These mutations are classified into six classes; on the one hand, the first three classes cause severe disease involvement in early childhood, on the other hand, the Class IV, V and VI mutations cause minor severe disease in the same age. Nowadays, with therapeutic advances in CF management and competence of pediatricians, physicians of adults have to deal with two groups of CF patients: (i) adults diagnosed in childhood with severe mutations and (ii) adults who initiated symptoms in adulthood and with Class IV, V and VI mutations. The aim of this study was to analyze adults from a clinical center, treated as CF disease, screening the CFTR genotype and evaluating the clinical characteristics.
  
  
  METHODS
  Thirty patients followed as CF disease at the University Hospital were enrolled. After a complete molecular CFTR negative screening and sweat test levels between 40 and 59mEq/L, five patients were characterized as non-CF disease and were excluded. Molecular screening was performed by CFTR gene sequencing/MLPA or by specific mutation screening. Clinical data was obtained from medical records. The patients were divided into three groups: (1) patients with Class I, II and III mutations in two CFTR alleles; (2) genotype with at least one allele of Class IV, V or VI CFTR mutations and, (3) non-identified CFTR mutation+one patient with one allele with CFTR mutation screened (Class I).
  
  
  RESULTS
  There was an association of CFTR class mutation and sodium/chloride concentration in the sweat test (sodium: p=0.040; chloride: p=0.016), onset of digestive symptoms (p=0.012), lung function parameter (SpO2 - p=0.016), Bhalla score (p=0.021), age at diagnosis (p=0.008) and CF-related diabetes (p=0.029). There was an association between Pseudomonas aeruginosa chronic colonization (as clinical marker for the lung disease status) and lung impairment (FEV1% - p=0.027; Bhalla score - p=0.021), CF-related diabetes (p=0.040), chloride concentration in the sweat test (p=0.040) and chronic infection by microorganisms (Staphylococcus aureus - p=0.039; mucoid P. aeruginosa - p=0.001). There is no positive association with the status of other clinical markers and the CFTR genotype groups. For clinical association with pancreatic insufficiency (as clinical marker for digestive symptoms), no association was related.
  
  
  CONCLUSIONS
  The adults with CF diagnosed by sweat test have specific clinical and genotypic characteristics, being a population that should be studied to cause better future management. Some patients treated as CF disease by clinical symptoms, showed no disease, taking into account the sweat test and complete exon sequencing/MLPA screening.
authors.affiliation: Department of Genetics, Faculty of Medical Sciences, University of Campinas, Unicamp, P.O. Box: 6111, 13081-970 Campinas, SP, Brazil. Electronic address: luciana.bonadia@gmail.com.
authors.forename: Luciana Cardoso
authors.initials: LC
authors.lastname: Bonadia
authors.affiliation: Department of Genetics, Faculty of Medical Sciences, University of Campinas, Unicamp, P.O. Box: 6111, 13081-970 Campinas, SP, Brazil; Department of Pediatrics, School of Medical Sciences, University of Campinas, Unicamp, P.O. Box: 6111, 13081-970 Campinas, SP, Brazil. Electronic address: fernandolimamarson@hotmail.com.
authors.forename: Fernando Augusto
authors.initials: FA
authors.lastname: de Lima Marson
authors.affiliation: Department of Pediatrics, School of Medical Sciences, University of Campinas, Unicamp, P.O. Box: 6111, 13081-970 Campinas, SP, Brazil. Electronic address: dirceu.unicamp@gmail.com.
authors.forename: Jose Dirceu
authors.initials: JD
authors.lastname: Ribeiro
authors.affiliation: Department of Pneumology, Faculty of Medical Sciences, University of Campinas, Unicamp, P.O. Box: 6111, 13081-970 Campinas, SP, Brazil. Electronic address: ilma@mpc.com.br.
authors.forename: Ilma Aparecida
authors.initials: IA
authors.lastname: Paschoal
authors.affiliation: Department of Pneumology, Faculty of Medical Sciences, University of Campinas, Unicamp, P.O. Box: 6111, 13081-970 Campinas, SP, Brazil. Electronic address: corso@mpcnet.com.br.
authors.forename: Monica Corso
authors.initials: MC
authors.lastname: Pereira
authors.affiliation: Department of Pediatrics, School of Medical Sciences, University of Campinas, Unicamp, P.O. Box: 6111, 13081-970 Campinas, SP, Brazil. Electronic address: anferi@fcm.unicamp.br.
authors.forename: Antonio Fernando
authors.initials: AF
authors.lastname: Ribeiro
authors.affiliation: Department of Genetics, Faculty of Medical Sciences, University of Campinas, Unicamp, P.O. Box: 6111, 13081-970 Campinas, SP, Brazil. Electronic address: bertuzzo@fcm.unicamp.br.
authors.forename: Carmen Silvia
authors.initials: CS
authors.lastname: Bertuzzo
mesh_terms: D000293:Adolescent; D000328:Adult; D002712:Chlorides / Q000378:metabolism; D003550:Cystic Fibrosis / Q000235:genetics* / Q000382:microbiology / Q000473:pathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D011552:Pseudomonas Infections / Q000235:genetics* / Q000473:pathology; D017384:Sequence Deletion; D012720:Severity of Illness Index; D012964:Sodium / Q000378:metabolism; D013203:Staphylococcal Infections / Q000235:genetics* / Q000473:pathology; D013542:Sweat / Q000378:metabolism; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C505032:CFTR protein, human; D002712:Chlorides; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D012964:Sodium
keywords: CFTR; Cystic fibrosis; Mutation