Screening practices for mutations in the CFTR gene ABCC7

Cystic fibrosis transmembrane conductance regulator (CFTR) gene studies are now one of the most frequent activities in clinical molecular genetics lab oratories. The number of requests is growing, owing to the increasingly wid e range of recognized CFTR gene diseases (cystic fibrosis, congenital bilat eral absence of the vas deferens, disseminated bronchiectasis, allergic bro nchopulmonary aspergillosis and chronic pancreatitis), and the availability of efficient molecular tools for detecting mutations. A growing number of tests capable of simultaneously detecting several frequent CF mutations are being developed, and commercial kits are now available. The most recent ki ts detect nearly 90% of defective alleles in Caucasians, a rate high enough for carrier screening and for the majority of diagnostic requests. However , because of the wide variety of molecular defects documented in the CFTR g ene, only a limited number of laboratories have mastered the entire panoply of necessary techniques, while other laboratories have to refer certain ca ses to specialized centers with complementary and/or scanning tools at thei r disposal. A good knowledge of CFTR diseases and their molecular mechanism s, together with expertise in the various techniques, is crucial for interp reting the results. Diagnostic strategies must take into account the indica tion, the patient's ethnic origin, and the time available in the framework of genetic counseling. This review presents the methods most frequently use d for detecting CFTR gene mutations, and discusses the strategies most suit ed to the different clinical settings. Hum Mutat 15:135-149, 2000. (C) 2000 Wiley-Liss, Inc.