Background

The retinol binding protein 4 (RBP4) is essential in delivering retinol to the retinal pigment epithelium and normal functioning of the visual cycle. Homozygous mutations in the RBP4 gene lead to severe retinitis pigmentosa that is phenotypically indistinguishable from retinitis pigmentosa caused by other recessive mutations.

Methods

Case Report.

Purpose

To report a novel homozygous RBP4 c.67 C > T variant in a case of retinitis pigmentosa associated with severe childhood acne vulgaris.

Results

A 49-year old Caucasian man with a family history of retinitis pigmentosa, presented with low vision and night blindness from early childhood. Fundus examination showed findings typical of recessive retinitis pigmentosa. Next generation sequencing analysis revealed a novel homozygous RBP4 c.67 C > T variant. Examination of patient’s back showed widespread scaring and hyperpigmentation secondary to severe childhood-onset acne vulgaris. Patient’s affected brother, positive for the same homozygous variant, also had a history of severe acne vulgaris whereas the unaffected brother did not, confirming that mutations in RBP4 segregated with the acne vulgaris phenotype in this family.

Conclusions

We describe a case of retinitis pigmentosa associated with acne vulgaris and highlight the role of this systemic manifestation of retinol deficiency in confirming pathogenicity of the novel variant. Given the small size of the genomic RBP4 DNA (0.6kb), gene therapy using an adeno-associated viral vector with subretinal delivery has great potential to treat this severe childhood-onset blinding retinal disease. In addition, ubiquitous expression of RBP4 supports the development of in vitro functional assays to test the vector potency for clinical use.

中文翻译：

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与色素性视网膜炎和儿童寻常痤疮相关的视黄醇结合蛋白 4 (RBP4) 中一种新型纯合 c.67C>T 变体。

背景

视黄醇结合蛋白 4 (RBP4) 对于将视黄醇递送至视网膜色素上皮细胞和视觉周期的正常功能至关重要。RBP4 基因中的纯合突变导致严重的视网膜色素变性，其在表型上与其他隐性突变引起的视网膜色素变性无法区分。

方法

案例报告。

目的

报告一种新的纯合子 RBP4 c.67 C > T 变体与严重儿童寻常痤疮相关的视网膜色素变性病例。

结果

一名 49 岁的白人男性，有色素性视网膜炎家族史，从小就患有低视力和夜盲症。眼底检查显示典型的隐性视网膜色素变性表现。下一代测序分析揭示了一种新的纯合子 RBP4 c.67 C > T 变体。对患者背部的检查显示继发于严重的儿童期发病的寻常痤疮的广泛疤痕和色素沉着过度。患者受影响的兄弟，对相同的纯合变异呈阳性，也有严重的寻常痤疮病史，而未受影响的兄弟则没有，证实 RBP4 中的突变与该家族中的寻常痤疮表型分离。

结论

我们描述了一例与寻常痤疮相关的视网膜色素变性病例，并强调了这种视黄醇缺乏的全身表现在确认新变异的致病性方面的作用。鉴于基因组 RBP4 DNA 的体积较小 (0.6kb)，使用腺相关病毒载体和视网膜下递送的基因疗法具有治疗这种严重的儿童期发病的致盲性视网膜疾病的巨大潜力。此外，RBP4 的普遍表达支持体外功能测定的开发，以测试载体在临床上的效力。