Sterile alpha motif domain containing 7 (SAMD7) is a component of the Polycomb repressive complex 1, which inhibits transcription of many genes, including those activated by the transcription factor Cone-Rod Homeobox (CRX). Here we report bi-allelic mutations in SAMD7 as a cause of autosomal-recessive macular dystrophy with or without cone dysfunction. Four of these mutations affect splicing, while another mutation is a missense variant that alters the repressive effect of SAMD7 on CRX-dependent promoter activity, as shown by in vitro assays. Immunostaining of human retinal sections revealed that SAMD7 is localized in the nuclei of both rods and cones, as well as in those of cells belonging to the inner nuclear layer. These results place SAMD7 as a gene crucial for human retinal function and demonstrate a significant difference in the role of SAMD7 between the human and the mouse retina.

包含 7 (SAMD7) 的不育 α 基序结构域是Polycomb 抑制复合物 1的一个组成部分，该复合物抑制许多基因的转录，包括那些由转录因子 Cone-Rod Homeobox (CRX) 激活的基因。在这里，我们报告SAMD7的双等位基因突变是伴有或不伴有视锥细胞功能障碍的常染色体隐性黄斑营养不良的原因。其中四个突变影响剪接，而另一个突变是错义变体，它改变了 SAMD7 对 CRX 依赖性启动子活性的抑制作用，如体外测定所示。人视网膜切片的免疫染色显示，SAMD7 位于视杆细胞和视锥细胞的细胞核中，以及属于内核层的细胞的细胞核中。这些结果将SAMD7视为对人类视网膜功能至关重要的基因，并证明SAMD7在人类和小鼠视网膜中的作用存在显着差异