A study conducted by researchers from Brazil showed that high-throughput sequencing technology (HTS) could be useful to establish a definitive molecular diagnosis of cystic fibrosis (CF).

“HTS technology applied to the identification of pathogenic variants associated with the development of this disease allows for the introduction of therapy with CFTR modulators that favour better patient management,” the researchers wrote in the Journal of Cellular and Molecular Medicine. “Currently, HTS technology has represented a major advance in CF diagnosis, substituting traditional molecular methods, due to full genotypic screening, enabling the use of precision medicine in the treatment of patients with CF.”

The analysis identified 11 cystic fibrosis transmembrane conductance regulator (CFTR) variants and allowed for a definitive molecular diagnosis of CF in 31 of 37 patients (83.8%).

The most frequent pathogenic variant was c.1521_1523delCTT, a class 2 mutation, with 20 patients (54.1%) presenting as homozygous. In addition, 7 patients (18.9%) were compound heterozygous for c.1521_1523delCTT and c.2052_2053insA, c.11C>A, c.3846G>A, c.1766G>A, c.2989-3C>G, or c.3266G>A.

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Twenty-five patients (80.6%) with the c.1521_1523delCTT variant were eligible for treatment with drugs recently approved by the US Food and Drug Administration to correct the defective CFTR protein. Five patients aged 2 to 5 years who were homozygous c.1521_1523delCTT could benefit from combination therapy with lumacaftor/ivacaftor (Orkambi®). Moreover, 20 patients aged 6 years or older who had 2 copies of c.1521_1523delCTT and/or 1 copy of c.1766G>A could benefit from combination therapy with tezacaftor/ivacaftor (Symdeko®) or elexacaftor/tezacaftor/ivacaftor (Trikafta®). The triple combination was not an option for 2 patients under 6 years of age.

In addition, the researchers identified 3 patients homozygous for c.3266G>A, c.1083_1084insTATGA, or c.3718_2477C>T, and 1 compound heterozygous for c.1624G>T and c.2988+1G>A.


de Melo ACV, de Souza KSC, da Silva HPV, et al. Screening by high-throughput sequencing for pathogenic variants in cystic fibrosis: Benefit of introducing personalized therapies. J Cell Mol Med. 2022;26(23):5943-5947. doi:https://doi.org/10.1111/jcmm.17605