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Abstract：
OBJECTIVE: 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.
METHODS: 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.
RESULTS: All patients had nystagmus (n = 15) and 93.3% had photophobia (n = 14). In addition, all patients (n = 15) had poor VA. Hyperopia with astigmatism was observed in 93.3% (n = 14) and complete color blindness in 93.3% of the patients (n = 14). In the context of family history, both parents of all patients (n = 15) were genetic carriers, with a high consanguinity rate (82%, n = 9 families). Electroretinography showed cone dysfunction with normal rods in 66.7% (n = 10) and both cone-rod dysfunction in 33.3% (n = 5) patients. Regarding the genotypic features, 93% of patients had variants in CNGA3 (n = 14) categorized as pathogenic Class 1 (86.7%, n = 13). Further, 66.7% (n = 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%, n = 2), c.830G>A (6.6%, n = 1), and c. 822G >T (6.6%, n = 1).
CONCLUSIONS: Consanguinity and belonging to the same tribe are major risk factors for disease inheritance. The most common genotype was CNGA3 with the c.661C>T DNA variant. We recommend raising awareness among families and providing genetic counseling for this highly debilitating disease.
METHODS: 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.
RESULTS: All patients had nystagmus (n = 15) and 93.3% had photophobia (n = 14). In addition, all patients (n = 15) had poor VA. Hyperopia with astigmatism was observed in 93.3% (n = 14) and complete color blindness in 93.3% of the patients (n = 14). In the context of family history, both parents of all patients (n = 15) were genetic carriers, with a high consanguinity rate (82%, n = 9 families). Electroretinography showed cone dysfunction with normal rods in 66.7% (n = 10) and both cone-rod dysfunction in 33.3% (n = 5) patients. Regarding the genotypic features, 93% of patients had variants in CNGA3 (n = 14) categorized as pathogenic Class 1 (86.7%, n = 13). Further, 66.7% (n = 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%, n = 2), c.830G>A (6.6%, n = 1), and c. 822G >T (6.6%, n = 1).
CONCLUSIONS: Consanguinity and belonging to the same tribe are major risk factors for disease inheritance. The most common genotype was CNGA3 with the c.661C>T DNA variant. We recommend raising awareness among families and providing genetic counseling for this highly debilitating disease.
摘要：
目的：色盲是一种罕见的静止性视网膜疾病，主要影响视锥细胞。患有色盲的人表现为畏光，眼球震颤,视力下降（VA），和色盲。已经鉴定了负责色盲的多个基因(例如环核苷酸门控通道亚基α3[CNGA3]和激活转录因子6)。研究已经评估了基因治疗在色盲中的作用。因此,治疗和预防，表型和基因型的鉴定至关重要。这里,我们描述了沙特阿拉伯患者与色盲相关的临床表现和基因突变.
方法：本病例系列研究包括15例患者的临床表现，暗示着色盲，他们接受了眼科和系统评估。具有典型色盲表型的患者使用全外显子组测试进行遗传评估。
结果：所有患者有眼球震颤（n=15），93.3%有畏光（n=14）。此外,所有患者（n=15）的VA均较差。在93.3％（n=14）的患者中观察到有散光的远视，在93.3％的患者中观察到完全色盲（n=14）。在家族史的背景下，所有患者的父母（n=15）都是遗传携带者，血缘率高(82%，n=9个家庭）。视网膜电描记术在66.7％（n=10）的患者中显示出视锥功能障碍，在33.3％（n=5）的患者中显示出视锥功能障碍。关于基因型特征，93％的患者有CNGA3变异（n=14）分类为致病性1类（86.7％，n=13)。Further,66.7%(n=10)的患者也携带c.661C>TDNA变异。Further,这些突变的患者是纯合子.还鉴定出其他三个变体：c.1768G>A（13.3%，n=2),c.830G>A（6.6%，n=1),c。822G>T(6.6%，n=1)。
结论：血缘关系和属于同一部落是疾病遗传的主要危险因素。最常见的基因型是具有c.661C>TDNA变异的CNGA3。我们建议提高家庭的认识，并为这种高度衰弱的疾病提供遗传咨询。
方法：本病例系列研究包括15例患者的临床表现，暗示着色盲，他们接受了眼科和系统评估。具有典型色盲表型的患者使用全外显子组测试进行遗传评估。
结果：所有患者有眼球震颤（n=15），93.3%有畏光（n=14）。此外,所有患者（n=15）的VA均较差。在93.3％（n=14）的患者中观察到有散光的远视，在93.3％的患者中观察到完全色盲（n=14）。在家族史的背景下，所有患者的父母（n=15）都是遗传携带者，血缘率高(82%，n=9个家庭）。视网膜电描记术在66.7％（n=10）的患者中显示出视锥功能障碍，在33.3％（n=5）的患者中显示出视锥功能障碍。关于基因型特征，93％的患者有CNGA3变异（n=14）分类为致病性1类（86.7％，n=13)。Further,66.7%(n=10)的患者也携带c.661C>TDNA变异。Further,这些突变的患者是纯合子.还鉴定出其他三个变体：c.1768G>A（13.3%，n=2),c.830G>A（6.6%，n=1),c。822G>T(6.6%，n=1)。
结论：血缘关系和属于同一部落是疾病遗传的主要危险因素。最常见的基因型是具有c.661C>TDNA变异的CNGA3。我们建议提高家庭的认识，并为这种高度衰弱的疾病提供遗传咨询。
