6531 Distribution of CFTR pathogenic variants of cystic fibrosis patients in Bahrain

Objectives Cystic fibrosis (CF) is a rare multi-systemic recessive disorder. 1 The spectrum and frequencies of CFTR mutations causing CF varies among different populations in Europe and the Middle East, with varying phenotypes of the disease. 2 3 In this study, we characterised the distribution of CFTR mutations in a representative CF cohort in the Kingdom of Bahrain and identified the different phenotypes of CF in Bahrain, in comparison to other regions. Methods CFTR mutations and associated clinical information were drawn from a representative longitudinal cohort spanning the last three decades. We sequenced 56 cases that had one or both CFTR mutations unidentified. Results The incidence of CF in Bahrain based on data from last three decades is 1 in 9, 880 live births. Altogether 18 mutations were identified, 13 of which were not previously detected in Bahrain, 4 accounting for close to 100% of all population-specific alleles. The most common alleles comprise of c. 1911delG 2043delG; 22. 8%, c. 2988+1G>A 3120+1G>A; 16. 3%, c. 2989–1G>A 3121-G>A; 14. 1%, c. 3909C>G N1303K; 13. 0%, c. 1521₁523delCTT p. PheF508del; 7. 6%, as seen in figure 1. Two novel alleles, c. 743+2 T>C and c. 1733₁734del TA, were detected. Although the proportion of 1st cousin marriages in the Bahraini population has decreased from 77% to 50%, 3 4 the frequency of homozygosity in our cases is 67. 4%, thereby indicating that CF still occurs in large, often related, families. CF patients in Bahrain present with faltering growth, pancreatic insufficiency and classical sino-pulmonary manifestations, with most patients presenting with faltering growth as the initial diagnostic symptom. The median age at diagnosis is 6 months and mean age at death is 12. 9 ± 4. 3 years. Interestingly, two cases also suffer from sickle cell disease, which has only been reported once before in Saudi Arabia. 5 Conclusion The most common CFTR mutations and phenotypes in Bahrain were identified, enabling more precise diagnosis, introduction of neonatal screening and targeted therapies beyond CFTR modulators. References Boek KD. Cystic fibrosis in the year 2020: a disease with a new face. Acta Pediatrica, 2020. Banjar H, Tuleimat L, El Seoudi AA, et al. Genotype patterns for mutations of the cystic fibrosis transmembrane conductance regulator gene: a retrospective descriptive study from Saudi Arabia. Annals of Saudi Medicine, 2020. European Cystic Fibrosis Society, ECFS Patient Registry Annual Data Report, Denmark: European Cystic Fibrosis Society. 2020. Eskandarani HA. Cystic Fibrosis Transmembrane Regulator Gene Mutations in Bahrain. Journal of Tropical Pediatrics, 2002. Banjar H. Sickle Cell Disease and Cystic Fibrosis. Saudi Medical Journal, 2003.