Darki Faezeh, Fekri Sahba, Farhangmehr Shaghayegh, Ahmadieh Hamid, Dehghan Mohammad Hossein, Elahi Elahe
School of Biology, University College of Science, University of Tehran, Tehran, Iran.
Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
J Curr Ophthalmol. 2019 Mar 2;31(2):172-179. doi: 10.1016/j.joco.2019.01.007. eCollection 2019 Jun.
To report the genetic analysis of an Iranian Bietti crystalline dystrophy (BCD)-affected family, and to review previously reported mutations in the gene and assess the distribution of affected amino acids in the encoded protein.
The eleven exons of were sequenced in the DNA of the proband of the Iranian BCD family. The putative disease-causing variation was screened in all affected and non-affected members. BCD causing mutations previously reported in the literature were compiled, and positions of amino acids affected by nonsense and missense mutations were mapped onto the primary structure of the CYP4V2 protein.
C.1219G > T in that causes p.Glu407* was identified as cause of BCD in the Iranian family. The mutation segregated with disease status. Clinical presentations were similar among affected members, except that one patient presented with retinal macular hole. Twelve nonsense and 47 missense mutations in were compiled. Inspection of distribution of amino acids affected by the mutations suggested non-random distribution and clustering of affected amino acids in nine regions of the protein, including regions that contain the heme binding site, the metal binding site, and a region between these binding sites. The most C-terminus proximal nonsense mutation affected position 482.
This study presents results of the genetic analysis of an Iranian BCD family. Protein regions affected by mutations within the nine mutation clusters include regions well conserved among orthologous proteins and human CYP4 proteins, some of which are associated with known functions. The findings may serve to identify reasonable candidate gene region targets for gene editing therapy approaches.
报告一个受伊朗Bietti结晶状营养不良症（BCD）影响的家系的基因分析，并回顾该基因先前报道的突变情况，评估编码蛋白中受影响氨基酸的分布。
对伊朗BCD家系先证者的DNA进行该基因11个外显子的测序。在所有患病和未患病成员中筛查可能导致疾病的变异。汇总文献中先前报道的导致BCD的突变，并将无义突变和错义突变影响的氨基酸位置映射到CYP4V2蛋白的一级结构上。
在该基因中发现C.1219G>T导致p.Glu407*，被确定为伊朗家系中BCD的病因。该突变与疾病状态共分离。除一名患者出现视网膜黄斑裂孔外，患病成员的临床表现相似。汇总了该基因中的12个无义突变和47个错义突变。对受突变影响的氨基酸分布的检查表明，受影响的氨基酸在蛋白的9个区域呈非随机分布和聚集，包括含有血红素结合位点、金属结合位点以及这些结合位点之间的一个区域。最靠近C端的无义突变影响位置482。
本研究展示了一个伊朗BCD家系的基因分析结果。九个突变簇内受突变影响的蛋白区域包括直系同源蛋白和人CYP4蛋白中保守性良好的区域，其中一些与已知功能相关。这些发现可能有助于确定基因编辑治疗方法合理的候选基因区域靶点。
