Médecine pulmonaire et respiratoire

Cystic Fibrosis in the Genomic Era: CFTR Genotyping as a Diagnostic Test

Abstract

Chee Y Ooi

Our insight into cystic fibrosis (CF) disease and diseases associated with CF gene mutations has significantly increased in recent years, particularly after the discovery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene over two decades ago. This has resulted in a widened spectrum of phenotypic manifestations of CF ranging from the classic multisystem disease in infancy and early childhood to adults with single-organ manifestations of CF such as chronic sinopulmonary disease, pancreatitis and obstructive azoospermia. As a consequence, the diagnosis of CF can be difficult to establish or exclude. Extensive CFTR genotyping has been limited by the inability to interpret the functional and clinical significance of a large number of identified CFTR mutations. As identified CFTR mutations can either be “disease-causing”, “of varying clinical consequences”, “benign” or have unknown consequences, the identification of mutations on both alleles may be insufficient alone to confirm the diagnosis of CF. More recently though, the number of mutations recognized to be disease-causing was greatly expanded by the Clinical and Functional Translation of CFTR (CFTR2) project. This review article discusses the role and yield of CFTR mutation analysis in the diagnosis of CF.