Background

Sorsby Fundus Dystrophy is an inherited macular degeneration caused by pathogenic variants in the TIMP3 gene. Clinical exam findings typically drusen –like deposits beneath the RPE or reticular pseudo drusen deposits above the RPE with a majority of patients developing choroidal neovascularization.

Materials and Methods

Case report of two members of a family that present with atypical clinical exam findings. Protein modeling of the novel Y137CTIMP3 variant was performed and compared with other known variants.

Results

In this study we describe a father and son initially diagnosed with retinitis pigmentosa of unknown genetic origin. More recent genetic testing of the patients, identified a novel c.410A>G; p.Tyr137Cys variant of uncertain clinical significance in the Tissue Inhibitor of Metalloproteinase-3 (TIMP3) gene. The atypical clinical findings led us to compare the theoretical molecular effects of this variant on the TIMP3 protein structure and interactions with other proteins using homology modeling and machine learning predictions.

Conclusions

It is important to consider mutations in TIMP3 in atypical cases of Retinitis Pigmentosa particularly in the absence of known variants.

中文翻译：

---

与色素性视网膜炎样表型有关的新型TIMP3突变。

背景

Sorsby眼底营养不良是由TIMP3基因中的致病变异引起的遗传性黄斑变性。临床检查发现通常为玻璃疣，如RPE下方的沉积物或RPE上方的网状假性玻璃疣沉积物，大多数患者出现脉络膜新生血管。

材料和方法

出现非典型临床检查发现的家庭中两个成员的病例报告。进行了新型Y137CTIMP3变体的蛋白质建模，并将其与其他已知变体进行了比较。

结果

在这项研究中，我们描述了最初诊断为遗传来源未知的视网膜色素变性的父母。最近对患者进行的基因检测发现了一种新颖的c.410A> G；p.Tyr137Cys变体在金属蛋白酶3（TIMP3）组织抑制剂中的临床意义不确定。非典型的临床发现使我们使用同源性建模和机器学习预测比较了该变体对TIMP3蛋白质结构的理论分子作用以及与其他蛋白质的相互作用。

结论

在色素性视网膜炎的非典型病例中考虑TIMP3的突变非常重要，尤其是在没有已知变异的情况下。