Cystic fibrosis transmembrane conductance regulator mutations at a referral center for cystic fibrosis

J Bras Pneumol. Sep-Oct 2013;39(5):555-61. doi: 10.1590/S1806-37132013000500005.
[Article in English, Portuguese]

Abstract

Objective: To determine the frequency of six mutations (F508del, G542X, G551D, R553X, R1162X, and N1303K) in patients with cystic fibrosis (CF) diagnosed, at a referral center, on the basis of abnormal results in two determinations of sweat sodium and chloride concentrations.

Methods: This was a cross-sectional study involving 70 patients with CF. The mean age of the patients was 12.38 ± 9.00 years, 51.43% were female, and 94.29% were White. Mutation screening was performed with polymerase chain reaction (for F508del), followed by enzymatic digestion (for other mutations). Clinical analysis was performed on the basis of gender, age, ethnicity, pulmonary/gastrointestinal symptoms, and Shwachman-Kulczycki (SK) score.

Results: All of the patients showed pulmonary symptoms, and 8 had no gastrointestinal symptoms. On the basis of the SK scores, CF was determined to be mild, moderate, and severe in 22 (42.3%), 17 (32.7%), and 13 (25.0%) of the patients, respectively. There was no association between F508del mutation and disease severity by SK score. Of the 140 alleles analyzed, F508del mutation was identified in 70 (50%). Other mutations (G542X, G551D, R553X, R1162X, and N1303K) were identified in 12 (7.93%) of the alleles studied. In F508del homozygous patients with severe disease, the OR was 0.124 (95% CI: 0.005-0.826).

Conclusions: In 50% of the alleles studied, the molecular diagnosis of CF was confirmed by identifying a single mutation (F508del). If we consider the analysis of the six most common mutations in the Brazilian population (including F508del), the molecular diagnosis was confirmed in 58.57% of the alleles studied.

OBJETIVO:: Determinar a frequência de seis mutações (F508del, G542X, G551D, R553X, R1162X e N1303K) em pacientes com fibrose cística (FC) de um centro de referência, diagnosticados pela presença de duas dosagens de sódio e cloro no suor alteradas.

MÉTODOS:: Estudo de corte transversal com 70 pacientes com idade média de 12,38 ± 9,00 anos, sendo que 51,43% eram do sexo feminino, e 94,29% eram caucasoides. A triagem de mutações foi realizada pela técnica de reação em cadeia da polimerase (F508del), seguida por digestão enzimática (demais mutações). A análise clínica foi realizada utilizando as variáveis sexo, idade, etnia, manifestações pulmonares/digestivas e escore de Shwachman-Kulczycki (ESK).

RESULTADOS:: Todos os pacientes apresentaram manifestações pulmonares, e 8 não apresentaram manifestações digestivas. Os resultados do ESK evidenciaram doença leve, moderada e grave, respectivamente, em 22 (42,3%), 17 (32,7%) e 13 (25,0%) pacientes. Não houve associação da mutação F508del com o grau de doença pelo ESK. Dos 140 alelos analisados, a mutação F508del foi identificada em 70 (50%). As demais mutações (G542X, G551D, R553X, R1162X e N1303K) foram identificadas em 12 (7,93%) dos alelos analisados. Em pacientes homozigotos F508del com doença grave, a OR foi de 0,124 (IC95%: 0,005-0,826).

CONCLUSÕES:: O diagnóstico molecular de FC foi confirmado pela identificação de apenas uma mutação (F508del) em 50% dos alelos estudados. Se considerarmos a análise das seis mutações de maior frequência na população brasileira (incluindo F508del), o diagnóstico molecular foi confirmado em 58,57% dos alelos analisados.

MeSH terms

  • Adolescent
  • Adult
  • Alleles*
  • Brazil
  • Child
  • Child, Preschool
  • Cross-Sectional Studies
  • Cystic Fibrosis / diagnosis
  • Cystic Fibrosis / genetics*
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
  • Female
  • Homozygote
  • Humans
  • Male
  • Mass Screening
  • Middle Aged
  • Molecular Diagnostic Techniques / methods
  • Mutation / genetics
  • Polymerase Chain Reaction / methods
  • Secondary Care Centers
  • Sequence Deletion / genetics*
  • Severity of Illness Index
  • Young Adult

Substances

  • Cystic Fibrosis Transmembrane Conductance Regulator