Sheremet N L, Grushke I G, Zhorzholadze N V, Ronzina I A, Mikaelyan A A, Kadyshev V V, Tanas A S, Anoshkin K I, Strelnikov V V
Research Institute of Eye Diseases, 11A Rossolimo St., Moscow, Russian Federation, 119021.
Research Centre for Medical Genetics, 1 Moskvorech'e St., Moscow, Russian Federation, 115522.
Vestn Oftalmol. 2019;135(4):10-18. doi: 10.17116/oftalma201913504110.
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.
评估ABCA4基因中存在p.G1961E突变的遗传性视网膜疾病（IRD）患者的表型-基因型相关性。
该研究纳入了20例ABCA4基因杂合状态下存在p.G1961E突变的患者，这些患者接受了全面的眼科检查，以及ABCA4、ELOVL4、PROM1、CNGB3基因编码序列和内含子相邻区域的高通量平行测序。
18例患者检测到p.G1961E突变处于杂合状态，同时伴有错义突变、剪接位点突变、移码重复和无义突变，2例患者未检测到第二个突变。4例患者的病程为2至5年，这使得无法评估动态的形态功能变化。在16例IRD病程为29±14年且ABCA4基因存在p.G1961E突变的患者中，13例患者的疾病进程相对较轻：视力为0.15±0.07，每年平均视力下降0.037±0.019，绝对/相对暗点在5至20°范围内，根据光学相干断层扫描（OCT），黄斑区椭圆体光感受器区损失3.52±1.21mm。3例患者，包括1例ABCA4基因无第二个突变的患者，显示出更明显的变化。所有20例患者的多焦视网膜电图均有改变。在8例p.G1961E杂合状态并伴有复合突变p.[L541P;A1038V]的患者中的7例，以及2例无第二个突变的患者中，全视野视网膜电图（Ganzfeld；ffERG）有不同程度的变化（异常）。
ABCA4基因中的常见突变 - p.G1961E - 在81%的病例中与相对较轻的IRD病程相关，即使存在第二个严重突变。然而，在罕见情况下，可观察到p.G1961E突变患者的IRD表型更为严重，这可能与其他遗传因素有关。在p.G1961E杂合状态并伴有p.[L541P;A1038V]的患者中，发现了ffERG变化（异常）。
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