Clin Genet 1999: 55: 496–497 Printed in Ireland. All rights reser6ed Letter to the Editor Determination of the prevalence of cystic fibrosis in the United Arab Emirates by genetic carrier screening To the Editor : The prevalence of cystic fibrosis (CF) in the United Arab Emirates (UAE) is unknown. Our previous work indicated that that two mutations, DF508 and S549R(T  G), account for 46 out of 52 (88%) CF alleles and characterize 95% (18 out of 19) of the affected families that have been referred to us (1). All patients that we investigated were ho- mozygous for either of the two mutations: 16 CF patients (who were of Bedouin origin) were S549R(T  G) homozygotes and 7 patients (who were of Baluch lineage) were DF508 homozygotes (1). In light of these observations, we designed a pilot study aimed at screening CFTR genes of a random sample of the indigenous UAE population for asymptomatic S549R(T  G) and DF508 car- rier status, with a view to estimating the prevalence of CF in this country. The sample population for this study comprised 400 unrelated UAE nationals (200 males and 200 females), who were out-patients of Tawam Hospi- tal, Al Ain (Abu Dhabi Emirate) who had con- sulted because of minor ailments. Great care was taken to ensure that all subjects of this study were unrelated. Detection of DF508 was carried out by non-de- naturing polyacrylamide gel electrophoresis (PAGE). PCR reactions were performed on 500 ng DNA samples using primers and conditions previ- ously described (1, 2). Mutation S549R is localized in exon 11 (T  G at nucleotide 1779) and alters a Dra III restriction site. Detection of the mutation was carried out routinely by Dra III restriction endonuclease analysis of exon 11 PCR products, which were generated using CGCF11 (3) without a GC-tail as the sense primer and CF11 (3) as the anti-sense primer (Fig. 1). 500 ng of PCR products was digested overnight at 37°C with 5 U of Dra III (New England Biolabs) into a final volume of 20 ml. Restriction digests were then dried down to 8 ml and loaded on 8 cm long, 6.5% non-denaturing polyacrylamide gels (Hoefer Scientific Instruments, San Francisco, CA); electrophoreses were carried out at 75 V for 1.5 h. Presence of suspected DF508 and S549R(T  G) mutants alleles was confirmed by sequencing analyses according to protocols that have been described elsewhere (3). Screening of the 800 chromosomes led to the detection of six carriers: four individuals were S549R(T  G) heterozygotes and two were DF508 heterozygotes (Table 1). The estimated frequencies of carriers of each of the two mutations in the population are thus: S549R(T  G), 1:100; DF508, 1:200. Given that DF508 and S549R(T  G) muta- tions characterize 95% of families (1), however, the estimated carrier frequency of any CF mutation in the population of UAE nationals is [6 × (100/95)]/ 400 = 1:63. If we assume that genotype frequencies occur in Hardy – Weinberg proportions, the esti- mated frequency of affected CF subjects in the Emirati population is 1:15876. Our estimates rely on small numbers – 26 CF patients and 6 asymptomatic carriers in a sample size of 400 – and we remain cautious with their interpretation. Furthermore, a population bias is possibly introduced by the organization of the UAE indigenous society into tribes, several mem- bers of which still live in remote desert areas. In the sample population recruited for this study, we could therefore have missed out isolated affected families. For this reason, the predicted CF preva- lence of 1:15876 amongst Emirati is probably a conservative estimate. Although the value of genetic testing is clear, the perception of genetic screening varies but there now seems to be general agreement across coun- tries that the pendulum has switched towards the side of seeking information on CF carrier status (4–6). The goals of carrier screening projects are two-fold: 1) to provide informed reproductive choices; and 2) to identify couples at risk in order to give them the opportunity to reduce the ‘pheno- typic load’ in affected families (6). At this point in time, introducing a large-scale carrier screening program for a disease such as CF (with a low prevalence at birth) is considered premature at best 496