Screening for F508del as a first step in the molecular diagnosis of cystic fibrosis

Abstract

OBJECTIVE: To determine the relevance of screening for the F508del mutation of the cystic fibrosis transmembrane conductance regulator gene as a first step in the genetic diagnosis of cystic fibrosis (CF) by associating the genotype with various clinical variables. METHODS: We evaluated 180 CF patients regarding the F508del mutation. The clinical data were obtained from the medical records of the patients and from interviews with their parents or legal guardians. RESULTS: Of the 180 patients studied, 65 (36.1%) did not carry the F508del mutation (group 0 [G0]), 67 (37.2%) were F508del heterozygous (G1), and 48 (26.7%) were F508del homozygous (G2). All three groups showed associations with the clinical variables. Homozygosis was associated with younger patients, younger age at CF diagnosis, and younger age at the first isolation of Pseudomonas aeruginosa (PA), as well as with higher prevalence of pancreatic insufficiency (PI) and non-mucoid PA (NMPA) colonization. In comparison with G1+G2 patients, G0 patients were older; first experienced clinical symptoms, digestive disease, and pulmonary disease at an older age; were older at CF diagnosis and at first PA isolation; and had a lower prevalence of PI and meconium ileus, as well as of colonization by NMPA, mucoid PA, and Burkholderia cepacia. In G1 patients, values were intermediate for age at CF diagnosis; age at first PA isolation, first pulmonary symptoms, and first clinical manifestations; MPA colonization; and OR for PI. CONCLUSIONS: The identification of F508del in 63.9% of the patients studied showed that this can be a useful tool as a first step in the genetic diagnosis of CF. The F508del genotype was associated with clinical severity of the disease, especially with the variables related to CF onset.

Cystic fibrosis: Identification and frequency of mutations in a mixed population from a low‐income region in Northeastern Brazil

“…The results of our study revealed that despite the high degree of miscegenation of the study population, with 96% non‐white patients, the initial investigation of only F508del mutation determined the genotype of approximately 30% of patients. This finding corroborates with the proposal of an initial investigation searching only for F508del mutation, as suggested for patients from the Brazilian southeast . In our population, subsequent investigation for G542X and 3120 + 1G>A mutations expanded the genotype knowledge to 50% of patients.…”

“…This finding corroborates with the proposal of an initial investigation searching only for F508del mutation, as suggested for patients from the Brazilian southeast. 4 In our population, subsequent investigation for G542X and 3120 + 1G>A mutations expanded the genotype knowledge to 50% of patients. Thus, the establishment of a step wise protocol, with the research of only three mutations, can optimize the use of public health resources and increase the access to molecular diagnosis techniques.…”

A new insight into CFTR allele frequency in Brazil through next generation sequencing

“…In populations with a more homogenous CFTR mutation spectrum, targeted mutation panels are the most used genotyping strategy. In Brazil, Marson et al suggest the investigation of F508del for initial genetic screening of CF patients. Considering our finding of 38.8% of homozygosity for this mutation and an allelic frequency of 8.6‐48.7% of alleles in other Brazilian studies, this could be a cost‐effective strategy, avoiding the use of more expensive and complex molecular techniques in patients homozygous for F508del.…”

ADIPOR2 Polymorphisms in Cystic Fibrosis are Potential Modifiers of Clinical Severity

“…Cystic Fibrosis (CF) (MIM: 219700) presents as phenotypic heterogeneity of the clinical manifestations that are modulated by cystic fibrosis transmembrane regulator (CFTR) mutations [1,2], the environment and modifier genes [3][4][5]. Our group has studied the clinical modulation of CF by candidate modifier genes that influence drug responses, the evolution of the lung and digestive disease in CF, and CF-related comorbidities [6][7][8][9][10][11][12][13][14].…”