Orosz Orsolya, Rajta István, Vajas Attila, Takács Lili, Csutak Adrienne, Fodor Mariann, Kolozsvári Bence, Resch Miklós, Sényi Katalin, Lesch Balázs, Szabó Viktória, Berta András, Balogh István, Losonczy Gergely
Department of Ophthalmology, University of Debrecen, Debrecen, Hungary.
Institute for Nuclear Research, Hungarian Academy of Sciences, Debrecen, Hungary.
Invest Ophthalmol Vis Sci. 2017 Mar 1;58(3):1834-1842. doi: 10.1167/iovs.16-21405.
Rare interchange haplotypes in exon 3 of the OPN1LW and OPN1MW opsin genes cause X-linked myopia, color vision defect, and cone dysfunction. The severity of the disease varies on a broad scale from nonsyndromic high myopia to blue cone monochromatism. Here, we describe a new genotype-phenotype correlation attributed to rare exon 3 interchange haplotypes simultaneously present in the long- and middle-wavelength sensitive opsin genes (L- and M-opsin genes).
A multigenerational family with X-linked high myopia and cone dystrophy was investigated.
Affected male patients had infantile onset myopia with normal visual acuity and color vision until their forties. Visual acuity decreased thereafter, along with the development of severe protan and deutan color vision defects. A mild decrease in electroretinography response of cone photoreceptors was detected in childhood, which further deteriorated in middle-aged patients. Rods were also affected, however, to a lesser extent than cones. Clinical exome sequencing identified the LVAVA and MVAVA toxic haplotypes in the OPN1LW and OPN1MW opsin genes, respectively.
Here, we show that LVAVA haplotype of the OPN1LW gene and MVAVA haplotype of the OPN1MW gene cause apparently nonsyndromic high myopia in young patients but lead to progressive cone-rod dystrophy with deuteranopia and protanopia in middle-aged patients corresponding to a previously unknown disease course. To the best of our knowledge, this is the first report on the joint effect of these toxic haplotypes in the two opsin genes on chromosome X.
视蛋白基因OPN1LW和OPN1MW外显子3中罕见的互换单倍型会导致X连锁近视、色觉缺陷和视锥细胞功能障碍。疾病的严重程度差异很大，从非综合征性高度近视到蓝锥单色视。在此，我们描述了一种新的基因型-表型相关性，它归因于长波长和中波长敏感视蛋白基因（L-视蛋白基因和M-视蛋白基因）中同时存在的罕见外显子3互换单倍型。
对一个患有X连锁高度近视和视锥细胞营养不良的多代家族进行了研究。
受影响的男性患者在四十岁之前有婴儿期发病的近视，视力和色觉正常。此后视力下降，同时出现严重的红色和绿色色觉缺陷。儿童期检测到视锥光感受器的视网膜电图反应轻度下降，中年患者中进一步恶化。视杆细胞也受到影响，但其程度小于视锥细胞。临床外显子组测序分别在OPN1LW和OPN1MW视蛋白基因中鉴定出LVAVA和MVAVA毒性单倍型。
在此，我们表明OPN1LW基因的LVAVA单倍型和OPN1MW基因的MVAVA单倍型在年轻患者中导致明显的非综合征性高度近视，但在中年患者中导致伴有绿色盲和红色盲的进行性视锥-视杆营养不良，这与之前未知的病程相对应。据我们所知，这是关于这两种毒性单倍型在X染色体上的两个视蛋白基因中的联合作用的首次报道。
