Eye Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates; and Department of Ophthalmology, Cleveland Clinic Lerner College of Medicine of Case Western University, Cleveland, Ohio.
Retina. 2020 Jul;40(7):1429-1433. doi: 10.1097/IAE.0000000000002606.
Stargardt disease (On-Line Mendelian Inheritance In Man 242000, STGD1) is the most common inherited macular dystrophy. STGD1 is typically a young-adult-onset disease that is recurrently associated with the ABCA4 mutant allele G1961E in homozygosity or compound heterozygosity. The genetics of ABCA4-related retinopathy in the Arabian Gulf region have not been well-studied. This report reviews the experience of the Ocular Genetics Service at Cleveland Clinic Abu Dhabi with clinically diagnosed ABCA4-related retinopathy in Emirati patients who underwent genetic testing.
Retrospective case series (2016-2018, inclusive).
All 22 identified patients (19 families; 11 males, 11 females; first visual symptoms 5-33 years old) were found to harbor biallelic ABCA4 pathologic variants. There were 14 childhood-onset cases (onset before 18 years of age; 12 families; 7 males, 7 females; first visual symptoms from 5 to 12 years old, median 8)-all were homozygous, 11 for the same novel double mutant allele G1961E/L857P. Those who underwent electroretinography (8) had cone-rod rather than isolated macular dystrophy. There were 8 adult-onset cases (onset at or after 18 years of age; 7 families; 4 males, 4 females; first visual symptoms from 18 to 33 years old, median 22)-all were compound heterozygous, seven harboring the common G1961E mutant allele.
The molecular yield for biallelic ABCA4 pathogenic variants is high for clinically diagnosed ABCA4-related retinopathy in Emiratis (100% in this case series). Homozygosity for a novel complex allele G1961E/L857P causes a childhood-onset cone-rod dystrophy rather than the young-adult-onset macular dystrophy that is associated with G1961E alone. This G1961/L857P complex allele likely represents a founder effect for the region.
斯塔加特病（在线孟德尔遗传在线 242000，STGD1）是最常见的遗传性黄斑营养不良。STGD1 通常是一种青年发病的疾病，在纯合子或复合杂合子中反复与 ABCA4 突变等位基因 G1961E 相关。阿拉伯海湾地区 ABCA4 相关性视网膜病变的遗传学尚未得到很好的研究。本报告回顾了克利夫兰诊所阿布扎比眼科遗传学服务中心对接受基因检测的阿联酋患者中临床诊断为 ABCA4 相关性视网膜病变的经验。
回顾性病例系列（2016-2018 年，包括在内）。
所有 22 名确诊患者（19 个家庭；11 名男性，11 名女性；首次视觉症状为 5-33 岁）均携带双等位基因 ABCA4 病理变异。有 14 例儿童发病（发病年龄在 18 岁之前；12 个家庭；7 名男性，7 名女性；首次视觉症状从 5 岁到 12 岁，中位数为 8 岁）-均为纯合子，11 例为同一新的双突变等位基因 G1961E/L857P。那些接受视网膜电图检查的患者（8 例）表现为视锥-视杆营养不良而非孤立性黄斑营养不良。有 8 例成人发病（发病年龄在 18 岁或以上；7 个家庭；4 名男性，4 名女性；首次视觉症状从 18 岁到 33 岁，中位数为 22 岁）-均为复合杂合子，7 例携带常见的 G1961E 突变等位基因。
在本病例系列中，对于临床诊断为 ABCA4 相关性视网膜病变的阿联酋患者，双等位基因 ABCA4 致病性变异的分子检出率很高（100%）。新型复杂等位基因 G1961E/L857P 的纯合子导致儿童发病的视锥-视杆营养不良，而不是与 G1961E 单独相关的青年发病的黄斑营养不良。该 G1961/L857P 复杂等位基因可能代表该地区的一个起源效应。
