Introduction

We present two patients, the proband and the affected sibling, with biallelic CRB1 mutations leading to a macular dystrophy.

Case presentation

We present two patients, the proband and the affected sibling, with biallelic CRB1 mutations leading to a macular dystrophy. With 15 years of follow-up for the proband, we illustrate the natural history of CRB1 maculopathy based on clinical examination, multimodal imaging, and electrophysiology. In addition, we demonstrate the wide phenotypic spectrum of the condition with the affected sister harboring the same variants but with much milder phenotypic manifestations.

Conclusion

In addition to a previously described pathogenic variant, Ile167_Gly169del, one pathogenic missense variant in CRB1, Lys801Ter, not previously associated with macular dystrophy, is reported here. While CRB1 mutations have been more commonly described in retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA), we demonstrate that mutations in CRB1 can cause a maculopathy with initial features similar to fenestrated sheen macular dystrophy (FSMD) that later evolves into severe macular atrophy.

中文翻译：

---

CRB1 黄斑病变表现为有孔的光泽黄斑营养不良，随访 15 年

介绍

我们介绍了两名患者，先证者和受影响的兄弟姐妹，双等位基因 CRB1 突变导致黄斑营养不良。

案例展示

我们介绍了两名患者，先证者和受影响的兄弟姐妹，双等位基因 CRB1 突变导致黄斑营养不良。通过对先证者 15 年的随访，我们根据临床检查、多模态成像和电生理学说明 CRB1 黄斑病变的自然史。此外，我们展示了该病的广泛表型谱，受影响的姐妹具有相同的变体，但表型表现要温和得多。

结论

除了先前描述的致病性变异外，这里还报道了 Ile167_Gly169del，CRB1 中的一个致病性错义变异 Lys801Ter，以前与黄斑营养​​不良无关。虽然 CRB1 突变在色素性视网膜炎 (RP) 和 Leber 先天性黑蒙 (LCA) 中更常见，但我们证明 CRB1 突变可导致黄斑病变，其初始特征类似于有孔光泽黄斑营养不良 (FSMD)，后来演变为严重的黄斑萎缩。