Various somatic isocitrate dehydrogenase 1 (IDH1) gene variants have been reported to drive lower-grade gliomas and secondary glioblastomas. In the current study, we explored the IDH1 variants in the glioma biopsy samples of patients from Pakistan. We explored the incidence of isocitrate dehydrogenase 1 gene variants by hotspot sequencing in 80 formalin-fixed paraffin-embedded tissues of different types of glioma biopsy samples. Structural modeling of the identified variants in isocitrate dehydrogenase 1 protein was done to see their possible consequences. The frequently described p.Arg132 variants were not found in any of the glioma types. However, in our study, we identified nonsynonymous variants at the residues p.R109 and p.G136 in astrocytomas and p.R100 in oligodendroglioma. These variants are affecting a part of the conserved domain in isocitrate dehydrogenase 1. Both of p.R100 and p.R109 variants are rare and described before, whereas the p.G136 variant identified in this study has never been described previously. Structural modeling showed that variants of these residues would directly affect the substrate binding and hence the enzyme activity.

中文翻译：

---

巴基斯坦胶质瘤患者异柠檬酸脱氢酶1基因变异分析

据报道，各种体细胞异柠檬酸脱氢酶 1 (IDH1) 基因变异可驱动低级别胶质瘤和继发性胶质母细胞瘤。在当前的研究中，我们探索了来自巴基斯坦患者的神经胶质瘤活检样本中的 IDH1 变体。我们通过热点测序在不同类型胶质瘤活检样本的 80 个福尔马林固定石蜡包埋组织中探索了异柠檬酸脱氢酶 1 基因变异的发生率。对异柠檬酸脱氢酶 1 蛋白中已鉴定的变体进行了结构建模，以了解其可能的后果。在任何胶质瘤类型中均未发现经常描述的 p.Arg132 变体。然而，在我们的研究中，我们在星形细胞瘤中的 p.R109 和 p.G136 和少突胶质细胞瘤中的 p.R100 残基处发现了非同义变异。这些变体影响了异柠檬酸脱氢酶 1 中保守结构域的一部分。 p.R100 和 p.R109 变体都很罕见并且以前描述过，而本研究中鉴定的 p.G136 变体以前从未被描述过。结构模型表明，这些残基的变体将直接影响底物结合，从而影响酶活性。