Diagnostic contribution of molecular analysis of the cystic fibrosis transmembrane conductance regulator gene in patients suspected of having mild or atypical cystic fibrosis

Abstract

OBJECTIVE: To evaluate the diagnostic contribution of molecular analysis of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in patients suspected of having mild or atypical cystic fibrosis (CF). METHODS: This was a cross-sectional study involving adolescents and adults aged ≥ 14 years. Volunteers underwent clinical, laboratory, and radiological evaluation, as well as spirometry, sputum microbiology, liver ultrasound, sweat tests, and molecular analysis of the CFTR gene. We then divided the patients into three groups by the number of mutations identified (none, one, and two or more) and compared those groups in terms of their characteristics. RESULTS: We evaluated 37 patients with phenotypic findings of CF, with or without sweat test confirmation. The mean age of the patients was 32.5 ± 13.6 years, and females predominated (75.7%). The molecular analysis contributed to the definitive diagnosis of CF in 3 patients (8.1%), all of whom had at least two mutations. There were 7 patients (18.9%) with only one mutation and 26 patients (70.3%) with no mutations. None of the clinical characteristics evaluated was found to be associated with the genetic diagnosis. The most common mutation was p.F508del, which was found in 5 patients. The combination of p.V232D and p.F508del was found in 2 patients. Other mutations identified were p.A559T, p.D1152H, p.T1057A, p.I148T, p.V754M, p.P1290P, p.R1066H, and p.T351S. CONCLUSIONS: The molecular analysis of the CFTR gene coding region showed a limited contribution to the diagnostic investigation of patients suspected of having mild or atypical CF. In addition, there were no associations between the clinical characteristics and the genetic diagnosis.

Cystic fibrosis in Latin America—Improving the awareness

“…For example, the equipment and expertise for the sweat chloride test are not universally available and the sweat conductivity test is frequently used instead. Although it is recognized that molecular testing is becoming increasingly useful, access to the necessary expertise and facilities for data interpretation using bioinformatics represents a significant obstacle in the near future [6,10]. Greater uniformity in the availability of diagnostic tests would be likely to further improve CF diagnosis rates across Latin America.…”

V232D mutation in patients with cystic fibrosis

“…A more recent study of 37 patients with suspected CF in Brazil reported 2 cases of CF with the V232D mutation (5.4%). [ 17 ] Both patients had F508del in the other allele.…”

“…Studies specifically analyzing the V232D mutation, however, have not described the pulmonary status of patients. [ 16 , 17 ]…”

Fibrosis Quística Atípica Y Enfermedad Del Cftr: A Propósito De Un Caso De Traqueobroncopatía Osteocondroplástica

“…En las mutaciones de clase IV y V existe producción de la proteína que mantiene cierta actividad residual y están asociadas a suficiencia pancreática y enfermedad más leve (1,2,4,7,8). La contribución de estas diferentes variantes alélicas del gen CFTR han sido evaluadas mediante estudios de correlación genotipo-fenotipo, con respecto a la variabilidad clínica o al grado de compromiso funcional (15,16). La mutación clase IV resulta en una normal cantidad de CFTR, con menor función de ella en la membrana apical, disminuyendo así la conductancia del cloro.…”