344 A cluster of the cystic fibrosis transmembrane regulator (CFTR) mutation S549R in the Sultanate of Oman

The mutational pattern of CFTR mutations is largely unknown in Oman and most other Arab countries. We describe initial investigations for establishing an Omani mutational panel by analyzing 22 alleles of non-related CF patients in a randomly selected subset of our patient cohort in North Al Bathina, Sultanate of Oman. The major disease-causing mutation is S549R. S549R was detected in 77.3% of the investigated alleles. In five alleles, the mutations could not be identified. One patient is a compound heterozygote with the mutation S549R and another yet-unidentified mutation. The most common Caucasian CFTR mutation, delF508, was absent in the investigated cohort. S549R eliminates the restriction site of DraIII in exon 11. Thus, this specific property can be utilized for fast and efficient prescreening and mutation detection upon clinical suspicion of CF. The phenotype of our S549R homozygotes is severe and characterized by failure to thrive with frequent pulmonary exacerbations. Analysis of fecal elastase in S549R homozygotes revealed severe exocrine pancreatic insufficiency. The average sweat conductivity and chloride concentration were 116±3.6 mmol/l and 102±5.7 mmol/l, respectively. The currently poor outcome of our CF patients with a life expectancy of 10.5±1.8 years cannot be attributed to S549R alone. Due to socio-cultural and medical-educational factors, 90% of the patients are below the 50 BMI percentile of the WHO child growth chart.