A recent study describes a new assay, CFseq, that uses dried blood spots to screen for defects in the gene underlying cystic fibrosis (CF) in newborns, and allows for comprehensive, specific, and rapid early detection of the disease.
The study, “Next-Generation Molecular Testing of Newborn Dried Blood Spots for Cystic Fibrosis,” was published in The Journal of Molecular Diagnostics.
CF is a genetic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Early detection of mutations in the Cftr gene is essential for prompt management of this debilitating disease, and genetic screening in newborns is required in many countries. However, effective screening on a large scale has often failed due to time length and high costs.
Researchers in the study describe a new assay, CFseq, for sequencing the Cftr gene that is both highly sensitive and specific, but also rapid (less than three days) and cost-effective. The assay allows a comprehensive CFTR gene analysis from dried blood spots, the common tested specimen from newborns. The method is based on optimized dried blood spots sample processing and DNA extraction, and performs a comprehensive analysis of the Cftr gene, including the detection of single-nucleotide variants, insertions, and deletions (including large deletions), and genomic copy number variations.
Moreover, the assay is low cost, does not required a lot of handling, and is ease to implement, all crucial features for its introduction in general clinical molecular laboratories equipped to perform next-generation sequencing testing.
The researchers concluded by highlighting that the CFseq assay could effectively replace all current CF genetic newborn screening and diagnostic assays. Potentially, it could also replace large deletions assays, such as multiplex ligation-dependent probe amplification, but this still needs further validation.
In CF, the defected or absent CFTR protein leads to the buildup of thick mucus, primarily in the lungs but also in other organs, including pancreas, liver, kidneys, and intestine. Mucus accumulation in the lungs clogs airways, creating a perfect environment for bacteria growth. As a result, patients with CF are burdened with recurrent infections, leading to lung damage and, eventually, respiratory failure.