title: Severe phenotype in an apparent homozygosity caused by a large deletion in the CFTR gene: a case report.
abstract: BACKGROUND
  Over 1900 mutations have been identified in the cystic fibrosis conductance transmembrane regulator gene, including single nucleotide substitutions, insertions, and deletions. Unidentified mutations may still lie in introns or in regulatory regions, which are not routinely investigated, or in large genomic deletions, which are not revealed by conventional molecular analysis. The apparent homozygosity for a rare, cystic fibrosis conductance transmembrane regulator mutation screened by standard molecular analysis should be further investigated to confirm if the mutation is in fact homozygous. We describe a patient presenting with an apparent homozygous S4X mutation.
  
  
  METHODS
  A 13-year-old female patient of African descent with clinical symptoms of classic cystic fibrosis and a positive sweat test (97 mEq/L, diagnosed at age 3 years) presented with pancreatic insufficiency and severe pulmonary symptoms (initial lung colonization with Pseudomonas aeruginosa at age 4 years; forced vital capacity: 69%; forced expiratory volume: 51%; 2011). Furthermore, she developed severe acute lung disease and recurrent episodes of dehydration requiring hospitalization. The girl carried the CFTR mutation S4X in apparent homozygosity. However, further analysis revealed a large deletion in the second allele that included the region of the mutation. The deletion that we describe includes nucleotides 120-142, which correspond to a loss of 23 nucleotides that abolishes the normal translation initiation codon.
  
  
  CONCLUSIONS
  This study reiterates the view that large, cystic fibrosis conductance transmembrane regulator deletions are an important cause of severe cystic fibrosis and emphasizes the importance of including large deletions/duplications in cystic fibrosis conductance transmembrane regulator diagnostic tests.
authors.forename: Raisa da Silva
authors.initials: Rda S
authors.lastname: Martins
authors.forename: Ana Carolina Proença
authors.initials: AC
authors.lastname: Fonseca
authors.forename: Franklyn Enrique Samudio
authors.initials: FE
authors.lastname: Acosta
authors.forename: Tania Wrobel
authors.initials: TW
authors.lastname: Folescu
authors.forename: Laurinda Yoko Shinzato
authors.initials: LY
authors.lastname: Higa
authors.forename: Izabela Rocha
authors.initials: IR
authors.lastname: Sad
authors.forename: Célia Regina Moutinho de Miranda
authors.initials: CR
authors.lastname: Chaves
authors.forename: Pedro Hernan
authors.initials: PH
authors.lastname: Cabello
authors.affiliation: Laboratório de Genética Humana, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Pavilhão Leônidas Deane sala 611, CEP: 21040-360 Avenida Brasil 4365, Rio de Janeiro, Brazil. gkalil.fiocruz@gmail.com.
authors.forename: Giselda Maria Kalil
authors.initials: GM
authors.lastname: Cabello
mesh_terms: D000293:Adolescent; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006720:Homozygote; D006801:Humans; D010641:Phenotype
chemical_list: C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator