Medical Genetics and Molecular Medicine Department, Medical school, Mashhad University of Medical Sciences, Mashhad, Iran.
Medical Genetics Research Center, Medical School, Mashhad University of Medical Sciences, Mashhad, Iran.
Clin Exp Dent Res. 2021 Aug;7(4):568-573. doi: 10.1002/cre2.387. Epub 2021 Feb 14.
In this study, we analyzed the whole exomes of CTSC gene in a family with history of PLS.
Genomic DNA was extracted from peripheral blood and genotype analysis was performed. The mutated protein sequence was used to find the best possible tertiary structure for homology modeling. The homology modeling of the novel mutation was then performed using the online Swiss-Prot server. The results were also analyzed for to verify its validity.
The analysis of CTSC gene elucidated a novel insertion GAC. The novel mutation was proved by analyzing 50 healthy control volunteers. Modeling of the novel found mutation in CTSC gene revealed structural defects that may have caused the functional abnormalities.
The structural analysis of the mutated protein model identifies changes in the stereo-chemical and the energy level of the mutated protein. Since this protein play a role in the activation of granule serine proteases from cytotoxic T lymphocytes, natural killer cells, mast cells, such structural defects may lead to its malfunction causing dysfunctioning of immune defense mechanisms.
在这项研究中，我们分析了一个有 PLS 病史的家族的 CTSC 基因的外显子组。
从外周血中提取基因组 DNA，并进行基因型分析。突变蛋白序列用于寻找同源建模的最佳可能三级结构。然后使用在线 Swiss-Prot 服务器对新型突变进行同源建模。还对结果进行了分析以验证其有效性。
对 CTSC 基因的分析揭示了一个新的插入 GAC。通过分析 50 名健康对照志愿者证实了新型突变。对 CTSC 基因中新型发现突变的建模揭示了可能导致功能异常的结构缺陷。
突变蛋白模型的结构分析确定了立体化学和突变蛋白能量水平的变化。由于该蛋白在细胞毒性 T 淋巴细胞、自然杀伤细胞、肥大细胞中颗粒丝氨酸蛋白酶的激活中起作用，这种结构缺陷可能导致其功能失常，从而导致免疫防御机制的功能障碍。
