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Cystic fibrosis (CF) is the most common life-limiting genetic disease in the white population. There are approximately 30,000 people with CF living in the United States,1 and there are approximately 70,000 people with CF worldwide.1 CF predominantly affects people of white descent, but it can occur in people of all races and ethnicities (Table 1). When first described in the 1930s, most children with CF died in infancy, but due to therapeutic gains the median predicted age of survival increased from age 28 years in 1986 to age 47.7 years in 2016 (Figure 1), and now 52.7% of people with CF are adults.1
Pathophysiology
Cystic fibrosis transmembrane conductance regulator (CFTR) plays a critical role in regulation of ion flow across cell membranes. Loss of CFTR expression or function affects multiple organ systems.2 Although CF is a multisystem disease, the primary organ systems affected are the pancreas and the lungs. Mucus obstruction of pancreatic ducts results in pancreatic insufficiency and malabsorption. In the lungs, loss of CFTR function results in abnormal mucus detachment, loss of the airway surface liquid layer, and impaired innate immunity. Other complications are shown in Table 2.
Genetics
CF is an autosomal recessive disease caused by mutations in the CFTR gene, which is located on chromosome 7q. More than 2,000 CFTR mutations has associated with a CF phenotype are known, but they are not all associated with disease liability. The Clinical and Functional Translation of CFTR project (known as CFTR2) is a worldwide effort to assign the disease liability to CFTR sequence variants.3 CFTR2 classifies mutations into four categories: (1) CF-causing, (2) mutations with varying clinical consequences (MVCC), (3) not CF-causing, and (4) unknown. Parents of children with CF are asymptomatic carriers. If both parents are carriers for a CFTR gene mutation, with each pregnancy there is a 25% chance of having a child with CF and a 50% chance of having a child who is a carrier. People who are carriers of CF have no manifestations of CF and no known survival benefit.
Diagnosis and Newborn Screening
Diagnosis of CF requires the presence of two known CF-causing mutations in addition to clinical symptoms or evidence of CFTR dysfunction.4 The CF Foundation diagnosis guidelines.4 recommend measurement of...