Congenital cone-rod synaptic disorder (CRSD), also known as incomplete congenital stationary night blindness (iCSNB), is a non-progressive inherited retinal disease (IRD) characterized by night blindness, photophobia, and nystagmus, and distinctive electroretinographic features. Here, we report bi-allelic RIMS2 variants in seven CRSD-affected individuals from four unrelated families. Apart from CRSD, neurodevelopmental disease was observed in all affected individuals, and abnormal glucose homeostasis was observed in the eldest affected individual. RIMS2 regulates synaptic membrane exocytosis. Data mining of human adult bulk and single-cell retinal transcriptional datasets revealed predominant expression in rod photoreceptors, and immunostaining demonstrated RIMS2 localization in the human retinal outer plexiform layer, Purkinje cells, and pancreatic islets. Additionally, nonsense variants were shown to result in truncated RIMS2 and decreased insulin secretion in mammalian cells. The identification of a syndromic stationary congenital IRD has a major impact on the differential diagnosis of syndromic congenital IRD, which has previously been exclusively linked with degenerative IRD.

先天性锥杆突触障碍（CRSD），也称为不完全先天性静止性夜盲症（iCSNB），是一种非进行性遗传性视网膜疾病（IRD），以夜盲、畏光和眼球震颤以及独特的视网膜电图特征为特征。在这里，我们报告了来自四个不相关家庭的七个受 CRSD 影响的个体的双等位基因RIMS2变异。除 CRSD 外，所有受影响个体均观察到神经发育疾病，并且在最年长的受影响个体中观察到葡萄糖稳态异常。RIMS2 调节突触膜胞吐作用。对成人大量和单细胞视网膜转录数据集的数据挖掘揭示了杆状光感受器中的主要表达，免疫染色证明了 RIMS2 定位于人视网膜外丛状层、浦肯野细胞和胰岛中。此外，无义变体被证明会导致 RIMS2 截短并减少哺乳动物细胞中的胰岛素分泌。综合征型静止性先天性 IRD 的识别对综合征型先天性 IRD 的鉴别诊断具有重大影响，此前该病仅与退行性 IRD 相关。