Diagnostic CFTR mutation analysis

The aim of this review is to provide an overview of the current scientific thinking on the molecular diagnosis of cystic fibrosis (CF). The paper describes current practices and technologies regarding the molecular analysis of the CF disease-causing mutations. So far, several mutations within the CFTR gene have been reported; all of them show huge frequency variability between different countries and also within the same country. Two different and subsequent levels of molecular tests can be offered to CF patients. The first consists of a rapid routinely screened panel of mutations that can be articulated on the basis of the regional prevalence. The second level refers to a scanning of the entire coding region of the CFTR gene including the exon/intron junctions and a large deletion analysis for detecting those mutations escaping from sequence analysis. Second-level analysis permits an increase in the detection rate to about 10%. Internal and external quality controls must always be adopted to obtain a good quality standard. Several innovative and elaborate technologies have been developed in different laboratories to increase the percentage of CF alleles that are detectable. Once this goal is reached, a more accurate calculation of risk recurrence will improve and strengthen the value of the genetic counselling, helping CF families in their reproductive options.