Citywide premarital genomic screening in a Middle Eastern population

Here we describe the feasibility and first implementation of a mandatory, citywide premarital genomic screening program comprising the sequencing of 782 genes, implicated in autosomal recessive disorders, in prospective couples enrolled through 18 primary healthcare centers throughout Dubai city. Since program inception, 1,000 couples have undergone testing, and 79 (8%, 95% confidence interval: 6.4-9.7) were identified as carriers of disease-causing variants in the same gene and, therefore, at risk of having affected children. This rate was significantly higher than that reported in the Australian Mackenzie's Mission study (3.9%; P < 0.0001). Although risk for hemoglobinopathies was most common, 59% of at-risk couples carried variants in 33 other genes. Of the 158 carriers, four (2.5%, 95% confidence interval: 1.0-6.3) were incidentally found to be homozygous for a pathogenic variant, indicating that they would be affected. Of the 79 at-risk couples, 63 (80%) elected to proceed with marriage while considering government-funded reproductive interventions, whereas 16 (20%) chose not to proceed. These findings underscore the feasibility and clinical utility of premarital genomic screening as part of a national strategy to reduce the burden of rare diseases.