[Phenotype-genotype correlations in patients with inherited retinal diseases with p.G1961E mutation in the ABCA4...

To evaluate phenotype-genotype correlations in patients with inherited retinal diseases (IRD) with mutation p.G1961E in the ABCA4 gene.

The study included 20 patients with p.G1961E mutation in the heterozygous state in the ABCA4 gene who underwent complete ophthalmic examination, as well as high-performance parallel sequencing of the coding sequences and adjacent areas of the introns of the ABCA4, ELOVL4, PROM1, CNGB3 genes.

The p.G1961E mutation was detected in heterozygous state with missense mutations, splice site mutations, a frameshift duplication, and a nonsense mutation in 18 patients, a second mutation was not detected in 2 patients. The duration of the disease in 4 patients was 2-5 years, which made it impossible to assess the morphofunctional changes in dynamics. In 13 of the 16 patients with IRD duration of 29±14 years and p.G1961E mutation in the ABCA4 gene the course of the disease was relatively mild: visual acuity of 0.15±0.07, loss of visual acuity averaging 0.037±0.019 per year, absolute/relative scotoma within 5-20°, and 3.52±1.21 mm loss of ellipsoid photoreceptor zone in the macular area according to OCT. In 3 patients, including one without a second mutation in the ABCA4 gene, better pronounced changes were revealed. Multifocal electroretinogram was altered in all 20 cases. In 7 of the 8 patients with p.G1961E in the heterozygous state in combination with complex mutation p.[L541P;A1038V], as well as in 2 patients without a second mutation, full-field electroretinography (Ganzfeld; ffERG) had changes (abnormalities) of varying intensity.

A frequent mutation in the ABCA4 gene - p.G1961E - is associated with a relatively mild course of IRD in 81% of cases, even in the presence of a second, severe mutation. However, in rare cases a more severe phenotype of the IRD in patients with p.G1961E mutation can be observed, which may be associated with other genetic factors. In patients with the p.G1961E mutation in heterozygous state with p.[L541P;A1038V], ffERG changes (abnormalities) were revealed.