Is n965S a common ABCA4 variant in Stargardt-related retinopathies in the Danish population?
Our study is the first mutation analysis of Stargardt-related retinopathies in a large cohort of patients from a Scandinavian population. The mutation detection rate, performed with an array-based technique, was comparable to that of other microarray-based ABCA4 studies as well as studies using more laborious techniques involving screening methods followed by sequencing. Four out of five of the most prevalent ABCA4 mutations are reported to be frequent in other Western European populations as well. However, the prevalence of the most common Danish mutation, N965S, significantly deviates from the one found in other studies. This underscores that the ABCA4 mutation spectrum within relatively stable populations might be skewed due to founder effects. The clinical spectrum of patients, who are either homozygous or compound heterozygous for the N965S mutation, indicates that this mutation has an early and profound effect on retinal function.
Baseline resistance may compromise the response to standard NNRTI-based first-line ART in 6% of patients in Lusaka, Zambia. Continuous resistance monitoring is warranted to maintain individual and population-level ART effectiveness.