310 Prevalence of CF and spectrum of CFTR mutations in the Portuguese population

In the Portuguese population the prevalence of CF is unknown, as well as, the spectrum of CFTR gene mutations. Objectives The main objective of this work was to evaluate the prevalence of CF and to establish the type and frequency of CFTR mutations in the Portuguese population. Methods DNA was extracted from buccal mucosa cells of 512 Portuguese children, using a commercial kit. CFTR gene analysis was performed by Sanger Sequencing in 206 samples and by Next Generation Sequencing in 306 samples. Results A total of 124 CF- and CFTR-related disorders (RD) mutations were identified. From de 512 samples analyzed, 90 had one mutation (17.6%) and 10 had two (1.9%). Taking into account only mutations included in the CFTR2 mutation database classified as CF-mutations or with varying consequences, the carrier frequency rate was 2.3%, being the most frequent mutation the p.Phe508del (0.98%). From the mutations detected, only the p.Phe508del is included in the screening commercial kits. The majority of mutations detected have been associated to CFTR-RD. The 5T allele (c.1210–12[5T]) was detected with an allelic frequency of 3.4%, followed by the complex allele p.Gly576Ala-p.Arg668Cys with 1.1%. Conclusion A wide spectrum of CFTR mutations was identified, confirming the highest CFTR allelic heterogeneity previously reported in Mediterranean countries. These results highlight the low power detection of the commercial kits for CFTR gene screening in our population. Additionally, this emphasizes the importance of the implemented Neonatal Screening Program last year in Portugal, as it facilitates the early diagnosis of symptom-free newborns carrying mutations.