Cystic fibrosis, molecular genetics for all life

Cystic fibrosis (CF) is the most frequent lethal autosomal recessive disorder among Caucasians (incidence: 1:2,500 newborn). In the last two decades CF prognosis considerably improved and many patients well survive into their adulthood. Furthermore, milder CF with a late onset was described. CF is a challenge for laboratory of molecular genetics that greatly contributes to the natural history of the disease since fetal age. Carrier screening and prenatal diagnosis, also by non-invasive analysis of maternal blood fetal DNA, are now available, and many labs offer preimplantation diagnosis. The major criticism in prenatal medicine is the lack of an effective multidisciplinary counseling that helps the couples to plan their reasoned reproductive choice. Most countries offer newborn screening that significantly reduce CF morbidity but different protocols based on blood trypsin, molecular analysis and sweat chloride cause a variable efficiency of the screening programs. Again, laboratory is crucial for CF diagnosis in symptomatic patients: sweat chloride is the diagnostic golden standard, but different methodologies and the lack of quality control in most labs reduce its effectiveness. Molecular analysis contributes to confirm diagnosis in symptomatic subjects; furthermore, it helps to predict the disease outcome on the basis of the mutation (genotype-phenotype correlation) and mutations in a myriad of genes, inherited independently by CF transmembrane conductance regulator (CFTR), which may modulate the clinical expression of the disease in each single patient (modifier genes). More recently, the search of the CFTR mutations gained a role in selecting CF patients that may benefit from biological therapy based on correctors and potentiators that are effective in patients bearing specific mutations (personalized therapy). All such applications of molecular diagnostics confirm the “uniqueness” of each CF patient, offering to laboratory medicine the opportunity to reposition the patient in the “core” of the medical process.