Cystic fibrosis carrier screening using next generation sequencing: A cautionary tale

Abstract

Adoption of next generation sequencing (NGS) for carrier screening can be a double-edged sword. The cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gene, of which homozygosity or compound heterozygosity for pathogenic variant(s) (i.e., mutations) result in CF, appears to be well suited for NGS carrier screening due to its tremendous size and number of reported mutations. Although the CFTR protein has only 1,480 amino acids, the CFTR gene spans over 189,000 base pairs, including 27 exons and 26 introns, and >2,000 pathogenic variants of the gene have been described in the coding sequences and in other regions.