ABSTRACT

Significance

The responsible genetic variants for occult macular dystrophy (OMD) were found at the predicted intrinsically disordered region (IDR) of the RP1L1 gene.

Purpose

We examined the phenotypes and genotypes of family members from OMD. In addition, the genetic characteristics of the RP1L1 gene in OMD were investigated.

Methods

Whole-exome sequencing was applied on two affected family members, and Sanger sequencing was performed on three members. The structural property of RP1L1 and pathogenic variants was analyzed using predictor of natural disordered regions (PONDR).

Results

Two affected members showed moderate visual impairment and relative central scotoma. The spectral domain optical coherence tomography (SD-OCT) images showed an absence of the interdigitation zone (IZ) and ellipsoid zone (EZ) in one case, and an obscure EZ line in the other case. A RP1L1 variant (c.3593 C > T, p.Ser1198Phe) was identified in two affected members but not in the unaffected member. The PONDR analysis showed that the region from p.1189 to p.1248 could be predicted to be an IDR in the RP1L1 molecule. And the p. Ser1198Phe variant showed significant reduction of PONDR score.

Conclusions

Although, the major pathogenic variant of OMD is p.Arg45Trp, multiple reports indicate that the region between p.1194 and p.1201 is another hot spot of OMD. The PONDR analysis predicted that the RP1L1 molecule is one of the intrinsically disordered proteins. It is speculated that the region around p.1200 is essential for the normal function of the RP1L1 molecule, and the missense variants of that area cause the development of OMD.

中文翻译：

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RP1L1基因的一个变异体，在预测的内在失调区域具有隐性黄斑营养不良。

摘要

意义

在RP1L1基因的预期内在无序区（IDR）中发现了隐匿性黄斑营养不良（OMD）的负责任遗传变异。

目的

我们检查了OMD家庭成员的表型和基因型。另外，还对OMD中RP1L1基因的遗传特性进行了研究。

方法

对两个受影响的家庭成员进行了全外显子测序，对三个成员进行了Sanger测序。RP1L1和致病性变异的结构特性使用自然无序区的预测因子（PONDR）进行了分析。

结果

两名受影响的成员表现为中度视力障碍和相对的中心性暗点。光谱域光学相干断层扫描（SD-OCT）图像显示在一种情况下不存在交叉指区（IZ）和椭圆体区域（EZ），而在另一种情况下则显示模糊的EZ线。甲RP1L1变体（c.3593 C> T，p.Ser1198Phe）在两个受影响的成员，但不是在未受影响的构件被确定。PONDR分析表明，从p.1189到p.1248的区域可以预测为RP1L1分子中的IDR。和p。Ser1198Phe变体显示PONDR得分显着降低。

结论

尽管OMD的主要致病变异是p.Arg45Trp，但许多报道表明p.1194和p.1201之间的区域是OMD的另一个热点。PONDR分析预测RP1L1分子是内在无序的蛋白质之一。据推测，p.1200周围的区域对于RP1L1分子的正常功能至关重要，而该区域的错义变异会导致OMD的发展。