Department of Ophthalmology, Federal University of Sao Paulo, Sao Paulo, Brazil.
Department of Biophysics, Federal University of Sao Paulo, Sao Paulo, Brazil.
Sci Rep. 2017 Aug 17;7(1):8654. doi: 10.1038/s41598-017-09035-1.
Inherited retinal dystrophies are characterized by progressive retina degeneration and mutations in at least 250 genes have been associated as disease-causing. CRB1 is one of many genes analyzed in molecular diagnosis for inherited retinal dystrophy. Crumbs homolog-1 protein encoded by CRB1 is important for cell-to-cell contact, polarization of epithelial cells and the morphogenesis of photoreceptors. Pathogenic variants in CRB1 lead to a huge variety of phenotypes ranging from milder forms of inherited retinal dystrophy, such as retinitis pigmentosa to more severe phenotypes such as Leber congenital amaurosis. In this study, seven novel likely-pathogenic variants were identified: four missense variants (p.Leu479Pro, p.Ala921Pro, p.Cys948Arg and p.Asp1031Asn), two frameshift deletions (c.2536_2542del7 and c.3460_3461delTG) and one frameshift indel variant (c.276_294delinsTGAACACTGTAC). Furthermore, two patients with cone-rod dystrophy due to mutations in CRB1 were reported, supporting previous data, in which mutations in CRB1 can also cause cone-rod dystrophy. Finally, our data suggested there was a direct relation between phenotype severity and the mutation effect on protein functionality in 15 Brazilian CRB1 patients.
遗传性视网膜营养不良的特征是进行性视网膜变性，至少有 250 个基因突变与疾病的发生有关。CRB1 是遗传性视网膜营养不良分子诊断中分析的众多基因之一。CRB1 编码的 Crb1 同源物-1 蛋白对于细胞间接触、上皮细胞极化和光感受器的形态发生很重要。CRB1 中的致病变体导致表型的多样性，从遗传性视网膜营养不良的较轻形式，如色素性视网膜炎到更严重的形式，如莱伯先天性黑蒙。在这项研究中，确定了七个新的可能致病变体：四个错义变体（p.Leu479Pro、p.Ala921Pro、p.Cys948Arg 和 p.Asp1031Asn），两个移码缺失（c.2536_2542del7 和 c.3460_3461delTG）和一个移码插入缺失变体（c.276_294delinsTGAACACTGTAC）。此外，还报道了两名因 CRB1 突变而患有 Cone-rod 营养不良的患者，这与先前的数据一致，其中 CRB1 的突变也可导致 Cone-rod 营养不良。最后，我们的数据表明，在 15 名巴西 CRB1 患者中，表型严重程度与突变对蛋白质功能的影响之间存在直接关系。
