Possible protective role of the ABCA4 gene c.1268A>G missense variant in Stargardt disease and syndromic retinitis pigmentosa in a Sicilian family: Preliminary data
Possible protective role of the ABCA4 gene c.1268A>G missense variant in Stargardt disease and syndromic retinitis pigmentosa in a Sicilian family: Preliminary data
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DOI：
10.3892/ijmm.2017.2917
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发表时间：
2017-04-01
影响因子：
5.4
通讯作者：
Sidoti, Antonina
中科院分区：
文献类型：
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作者：
D'Angelo, Rosalia;Donato, Luigi;Sidoti, Antonina
在视网膜色素变性形式中的眼科罕见疾病的广泛视野中，Stargardt病由于其异质性而逐渐发挥重要作用。在本研究中，我们的目的是支持两个相反的假设之一，关于杂合c.1268A>G错义变异的ABCA 4基因在Stargardt病和综合征性视网膜色素变性的致病或保护作用。本研究基于一个由三名成员组成的家族：先证者，54岁，患有高度近视、近视性脉络膜视网膜炎和视网膜营养不良;妻子，65岁，症状轻微;女儿，29岁，无症状。遗传咨询后，进行ABCA 4和RP 1基因分析。结果凸显了一个重要的遗传图景。发现先证者携带两种变异RP 1 SNP，rs 2293869（c.2953A>T）和rs61739567（c.6098G>A），以及四种RP 1多态性的野生型条件，rs 444772（c.2623G>A）和“热点”区域（外显子4）的三种SNP。相反，先证者的妻子表现出与丈夫相反的情况：分析的前四个SNP是纯合突变，而最后两个是野生型。关于ABCA 4基因，先证者证明了野生型条件。此外，妻子表现出ABCA 4 rs3112831（c.1268A>G）的杂合子状况。正如预期的那样，女儿提出了两个基因的所有变体的杂合性。总之，尽管ABCA 4基因的c.1268A>G错义变体经常被报道为疾病的病因，并且在其他情况下对疾病具有保护作用，但在我们的家族病例中，该变体似乎降低或延迟了Stargardt病的发病风险。
In the wide horizon of ophthalmologically rare diseases among retinitis pigmentosa forms, Stargardt disease has gradually assumed a significant role due to its heterogeneity. In the present study, we aimed to support one of two opposite hypotheses concerning the causative or protective role of heterozygous c.1268A>G missense variant of the ABCA4 gene in Stargardt disease and in syndromic retinitis pigmentosa. This study was based on a family consisting of three members: proband, age 54, with high myopia, myopic chorioretinitis and retinal dystrophy; wife, age 65, with mild symptoms; daughter, age 29, asymptomatic. After genetic counseling, ABCA4 and RP1 gene analysis was performed. The results highlighted an important genetic picture. The proband was found to carry two variant RP1 SNPs, rs2293869 (c.2953A>T) and rs61739567 (c.6098G>A), and, a wild-type condition for four RP1 polymorphisms, rs444772 (c.2623G>A) and three SNPs in the 'hot-spot' region, exon 4. The proband's wife, instead, showed an opposite condition compared to her husband: a homozygous mutated condition for the first four SNPs analyzed, while the last two were wild-type. Regarding the ABCA4 gene, the proband evidenced a wild-type condition. Furthermore, the wife showed a heterozygous condition of ABCA4 rs3112831 (c.1268A>G). As expected, the daughter presented heterozygosity for all variants of both genes. In conclusion, even though the c.1268A>G missense variant of the ABCA4 gene has often been reported as causative of disease, and in other cases protective of disease, in our family case, the variant appears to reduce or delay the risk of onset of Stargardt disease.