Background

Recent advances in genetic sequencing techniques have improved the overall diagnostic yield for finding genetic causes for inherited retinal dystrophies (IRD). Rod-cone dystrophy is the most common IRD and is characterized by the primary involvement of the rod photoreceptors. Over 80 causal genes have been identified so far giving clinicians insight into the pathogenesis. SLC4A7 encodes a sodium bicarbonate cotransporter responsible acid disposal which, within the retina, is prevalent in the photoreceptor synaptic terminals. Thus far, there have been no published reports of variants in this gene known to cause rod-cone dystrophy.

Material and Methods

Case report of a rod-cone dystrophy patient with a novel mutation in SLC4A7, whole exome sequencing with CLIA-certified NGS and Sanger confirmation, and, review of a SLC4A7 knockout mouse model phenotype.

Results

A 66-year-old male presented with slowly progressing night blindness, constricted visual field and relatively stable visual acuity. Fundus examination showed diffuse intraretinal pigment in the mid- and peripheral retina, diffuse retinal pigment epithelial atrophy, and intact macula in both eyes. There has been mild macular edema in both eyes which remained stable with the use of topical dorzolamide eyedrops. Whole exome sequencing found, and a subsequent vision panel confirmed, the pathogenic variant to be a homozygous frameshift mutation in SLC4A7 which results in termination of the protein.

Conclusions

We report a case of progressive rod-cone dystrophy caused by a novel mutation in SLC4A7, a gene coding the sodium bicarbonate cotransporter NBC3, underscoring the importance of ion homeostasis for photoreceptor function and maintenance.

中文翻译：

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SLC4A7基因的新突变导致常染色体隐性进行性杆状锥营养不良。

背景

基因测序技术的最新进展提高了寻找遗传性视网膜营养不良（IRD）遗传原因的总体诊断率。视锥细胞营养不良是最常见的IRD，其特征是视杆感光细胞的主要参与。迄今为止，已经鉴定出80多种因果基因，使临床医生能够深入了解其发病机理。SLC4A7编码负责碳酸氢钠共转运蛋白的酸处理，该处理在视网膜内普遍存在于感光突触末端。迄今为止，尚未公开已知该基因引起杆锥营养不良的变体的报道。

材料与方法

杆状锥营养不良患者的病例报告，该患者具有SLC4A7的新突变，带有CLIA认证的NGS和Sanger确认的全外显子组测序以及SLC4A7敲除小鼠模型表型的综述。

结果

一名66岁的男性表现为夜盲进展缓慢，视野狭窄和视力相对稳定。眼底检查显示视网膜中和周围视网膜弥漫性视网膜内色素沉着，双眼弥漫性视网膜色素上皮萎缩和完整黄斑。两只眼睛都出现了轻度的黄斑水肿，使用局部的多佐胺滴眼液可保持稳定。发现了完整的外显子组测序，随后的视觉研究小组确认，该病原体是SLC4A7中的纯合移码突变，导致该蛋白终止。

结论

我们报告一例由SLC4A7，编码碳酸氢钠共转运蛋白NBC3的基因的新型突变引起的进行性杆锥营养不良的病例，强调离子稳态对感光器功能和维持的重要性。