Danish Enam, Alhashem Amal, Aljehani Reham, Aljawi Anan, Aldarwish Manar M, Al Mutairi Fuad, Alfadhel Majid, Alrifai Muhammad T, Alobaisi Saif
Department of Ophthalmology, King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia.
Department of Pediatric, Division of Genetic and Metabolic Medicine, Prince Sultan Medical Military City, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.
Saudi J Ophthalmol. 2023 Sep 16;37(4):301-306. doi: 10.4103/sjopt.sjopt_108_23. eCollection 2023 Oct-Dec.
Achromatopsia is a rare stationary retinal disorder that primarily affects the cone photoreceptors. Individuals with achromatopsia present with photophobia, nystagmus, reduced visual acuity (VA), and color blindness. Multiple genes responsible for achromatopsia have been identified (e.g. cyclic nucleotide-gated channel subunit alpha 3 [CNGA3] and activating transcription factor 6). Studies have assessed the role of gene therapy in achromatopsia. Therefore, for treatment and prevention, the identification of phenotypes and genotypes is crucial. Here, we described the clinical manifestations and genetic mutations associated with achromatopsia in patients from Saudi Arabia.
This case series study included 15 patients with clinical presentations, suggestive of achromatopsia, who underwent ophthalmological and systemic evaluations. Patients with typical achromatopsia phenotype underwent genetic evaluation using whole-exome testing.
All patients had nystagmus ( = 15) and 93.3% had photophobia ( = 14). In addition, all patients ( = 15) had poor VA. Hyperopia with astigmatism was observed in 93.3% ( = 14) and complete color blindness in 93.3% of the patients ( = 14). In the context of family history, both parents of all patients ( = 15) were genetic carriers, with a high consanguinity rate (82%, = 9 families). Electroretinography showed cone dysfunction with normal rods in 66.7% ( = 10) and both cone-rod dysfunction in 33.3% ( = 5) patients. Regarding the genotypic features, 93% of patients had variants in ( = 14) categorized as pathogenic Class 1 (86.7%, = 13). Further, 66.7% ( = 10) of patients also harbored the c.661C>T DNA variant. Further, the patients were homozygous for these mutations. Three other variants were also identified: c.1768G>A (13.3%, = 2), c.830G>A (6.6%, = 1), and c. 822G >T (6.6%, = 1).
Consanguinity and belonging to the same tribe are major risk factors for disease inheritance. The most common genotype was with the c.661C>T DNA variant. We recommend raising awareness among families and providing genetic counseling for this highly debilitating disease.
全色盲是一种罕见的静止性视网膜疾病，主要影响视锥光感受器。全色盲患者表现出畏光、眼球震颤、视力下降和色盲。已鉴定出多个导致全色盲的基因（如环核苷酸门控通道亚基α3 [CNGA3] 和激活转录因子6）。研究评估了基因治疗在全色盲中的作用。因此，对于治疗和预防而言，识别表型和基因型至关重要。在此，我们描述了来自沙特阿拉伯患者中与全色盲相关的临床表现和基因突变。
本病例系列研究纳入了15例临床表现提示全色盲的患者，他们接受了眼科和全身评估。具有典型全色盲表型的患者采用全外显子组检测进行基因评估。
所有患者均有眼球震颤（n = 15），93.3%（n = 14）有畏光。此外，所有患者（n = 15）视力均较差。93.3%（n = 14）的患者有远视合并散光，93.3%（n = 14）的患者有完全色盲。在家族史方面，所有患者（n = 15）的父母均为基因携带者，近亲结婚率较高（82%，n = 9个家庭）。视网膜电图显示，66.7%（n = 10）的患者视锥功能障碍而视杆正常，33.3%（n = 5）的患者视锥 - 视杆均功能障碍。关于基因型特征，93%的患者（n = 14）在CNGA3中有被归类为致病性1类变异（86.7%，n = 13）。此外，66.7%（n = 10）的患者还携带c.661C>T DNA变异。此外，患者这些突变均为纯合子。还鉴定出其他三个变异：c.1768G>A（13.3%，n = 2）、c.830G>A（6.6%，n = 1）和c.822G>T（6.6%，n = 1）。
近亲结婚和属于同部落是疾病遗传的主要危险因素。最常见的基因型是携带c.661C>T DNA变异的CNGA3。我们建议提高家庭对此病的认识，并为这种高度致残性疾病提供遗传咨询。
