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The spectrum and the frequencies of <jats:italic>CFTR<\/jats:italic> mutations causing CF vary amongst different populations in Europe and the Middle East. In this study, we characterised the distribution of CF-causing mutations\u00a0(i.e. pathogenic variants in the \u00a0<jats:italic>CFTR<\/jats:italic>\u00a0gene) in a representative CF cohort from the Kingdom of Bahrain based on a three-decade-long analysis at a single tertiary centre. We aim to improve CF genetic diagnostics, introduce of CF neonatal screening and provide CFTR modulator therapy (CFTRm).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p><jats:italic>CFTR<\/jats:italic> genotyping\u00a0 and associated clinical information were drawn from a longitudinal cohort. We sequenced 56 people with CF (pwCF) that had one or both <jats:italic>CFTR<\/jats:italic> mutations unidentified and carried out comprehensive bioinformatic- and family-based segregation analyses of detected variants, including genotype\u2013phenotype correlations and disease incidence estimates. The study methodology could serve as a basis for other non-European CF populations with a high degree of consanguinity.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Altogether 18 CF-causing mutations\u00a0 were identified, 15 of which were not previously detected in Bahrain, accounting for close to 100% of all population-specific alleles. The most common alleles comprise c.1911delG [2043delG; 22.8%], c.2988+1G\u2009&gt;\u2009A [3120+1G&gt;A; 16.3%], c.2989-1G&gt;A [3121-1G&gt;A; 14.1%], c.3909C&gt;G [N1303K; 13.0%], and c.1521_1523delCTT [p.PheF508del; 7.6%]. Although the proportion of 1st cousin marriages has decreased to 50%, the frequency of homozygosity in our pwCF is 67.4%, thereby indicating that CF still occurs in large, often related, families. pwCF in Bahrain present with faltering growth, pancreatic insufficiency and classical sino-pulmonary manifestations. Interestingly, two pwCF also suffer from sickle cell disease. The estimated incidence of CF in Bahrain based on data from the last three decades is 1 in 9,880 live births.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>The most commonCF-causing\u00a0 mutations in Bahraini pwCF were identified, enabling more precise diagnosis, introduction of two-tier neonatal screening and fostering administration of CFTRm.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00438-024-02119-4","type":"journal-article","created":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T16:02:34Z","timestamp":1715702554000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Distribution of pathogenic variants in the CFTR gene in a representative cohort of people with cystic fibrosis in the Kingdom of Bahrain"],"prefix":"10.1007","volume":"299","author":[{"given":"Osama A. 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