Introduction to Molecular Cystic Fibrosis Testing

MUTATIONS ASSOCIATED WITH CYSTIC FIBROSIS AND DISEASE OUTCOMES Cystic fibrosis (CF) is one of the most common inherited diseases in the United States with an incidence of about 1 in 3,700 births.¹ CF is more common among Caucasians (1 in 2,500, with a carrier frequency of 1 in 25) than among other groups such as African Americans (1 in 15,000) or Asian Americans (1 in 31,000).²

Cystic fibrosis, inherited in an autosomal recessive manner, arises from mutations in the gene encoding the 1,480 amino acid-long cystic fibrosis transmembrane conductance regulator (CFTR) protein that functions as a membrane chloride channel. As a recessive disorder, an individual must inherit two defective CF genes, one from each parent, to have CF. The CF patient need not inherit two copies of the same mutation but may inherit two different CFTR mutations, a condition referred to as compound heterozygosity. A person having just one mutant gene will produce functional CFTR protein and will not have symptoms of CF but is considered a carrier. Each…

ABBREVIATIONS: ACMG = American College of Medical Genetics; ACOG = American College of Obstetrics and Gynecology; ASRs = analyte specific reagents; cAMP = cyclic adenosine-5′-monophosphate; CBAVD = congenital bilateral absence of the vas deferens; CF = cystic fibrosis; CFTR = cystic fibrosis transmembrane conductance regulator; CLSI = Clinical and Laboratory Standards Institute; FDA = United States Food and Drug Administration; IRT = immunoreactive trypsinogen; KB = kilo bases; NHGRI = National Human Genome Research Institute. PKA = protein kinase A; QC = quality control