PDF(Pubmed)
Abstract：
This study focused on the genetic screening of Myocilin (MYOC), Cytochrome P450 family 1 subfamily B member 1 (CYP1B1), Optineurin (OPTN), and SIX homeobox 6 (SIX6) genes in a family with coexistence of primary congenital glaucoma (PCG) and juvenile open-angle glaucoma (JOAG).
Sanger sequencing was used to examine the coding region of all four genes. Six different online available algorithms were used for the pathogenicity prediction of missense variant. Structural analysis was done using Garnier-Osguthorpe-Robson (GOR), PyMol, ChimeraX, and Molecular Dynamic (MD) Simulations (using Graphics Processing Unit (GPU)-enabled Desmond module of Schrödinger).
There were a total of three sequence variants within the family. All seven algorithms determined that a single mutation, G538E, in the OPTN gene is pathogenic. The loops connecting the strands became more flexible, as predicted structurally and functionally by pathogenic mutations. Mutations create perturbations and conformational rearrangements in proteins, hence impairing their functioning.
In this study, we describe a North Indian family in which members were having JOAG and PCG due to a rare homozygous/heterozygous mutation in OPTN. The coexistence of two types of glaucoma within a single pedigree suggests that certain OPTN mutations may be responsible for the onset of different glaucoma phenotypes.
Sanger sequencing was used to examine the coding region of all four genes. Six different online available algorithms were used for the pathogenicity prediction of missense variant. Structural analysis was done using Garnier-Osguthorpe-Robson (GOR), PyMol, ChimeraX, and Molecular Dynamic (MD) Simulations (using Graphics Processing Unit (GPU)-enabled Desmond module of Schrödinger).
There were a total of three sequence variants within the family. All seven algorithms determined that a single mutation, G538E, in the OPTN gene is pathogenic. The loops connecting the strands became more flexible, as predicted structurally and functionally by pathogenic mutations. Mutations create perturbations and conformational rearrangements in proteins, hence impairing their functioning.
In this study, we describe a North Indian family in which members were having JOAG and PCG due to a rare homozygous/heterozygous mutation in OPTN. The coexistence of two types of glaucoma within a single pedigree suggests that certain OPTN mutations may be responsible for the onset of different glaucoma phenotypes.
摘要：
■这项研究集中在Myocilin（MYOC）的遗传筛选上，细胞色素P450家族1亚家族B成员1(CYP1B1),视神经磷酸酶（OPTN），原发性先天性青光眼（PCG）和青少年开角型青光眼（JOAG）共存的家族中的六个同源异型框6（SIX6）基因。
■Sanger测序用于检查所有四个基因的编码区。六种不同的在线可用算法用于错义变体的致病性预测。使用Garnier-Osgusthorpe-Robson（GOR）进行结构分析，PyMol,ChimeraX,和分子动力学（MD）模拟（使用Schrödinger的图形处理单元（GPU）启用的Desmond模块）。
■该家族中总共有三个序列变体。所有七个算法都确定单个突变，G538E,在OPTN基因中具有致病性。连接股线的环变得更加灵活，正如致病性突变在结构和功能上预测的那样。突变在蛋白质中产生扰动和构象重排，从而损害他们的功能。
■在这项研究中，我们描述了一个北印度家族,其中成员由于OPTN中罕见的纯合/杂合突变而患有JOAG和PCG.单一谱系中两种类型的青光眼共存表明某些OPTN突变可能是不同青光眼表型发作的原因。
■Sanger测序用于检查所有四个基因的编码区。六种不同的在线可用算法用于错义变体的致病性预测。使用Garnier-Osgusthorpe-Robson（GOR）进行结构分析，PyMol,ChimeraX,和分子动力学（MD）模拟（使用Schrödinger的图形处理单元（GPU）启用的Desmond模块）。
■该家族中总共有三个序列变体。所有七个算法都确定单个突变，G538E,在OPTN基因中具有致病性。连接股线的环变得更加灵活，正如致病性突变在结构和功能上预测的那样。突变在蛋白质中产生扰动和构象重排，从而损害他们的功能。
■在这项研究中，我们描述了一个北印度家族,其中成员由于OPTN中罕见的纯合/杂合突变而患有JOAG和PCG.单一谱系中两种类型的青光眼共存表明某些OPTN突变可能是不同青光眼表型发作的原因。
