Yan Xiang, Xu Zihao, Chen Yue, Gao Langping, Jiang Zige, Liu Lexin, Wang Guozhen, Chen Xiangjun, Wu Chengpeng, Hu Lidan
Department of Urology, Pediatric Urolith Center, National Clinical Research Center for Child Health, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, China.
Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin, 300211, China.
Hum Cell. 2025 Jan 6;38(2):40. doi: 10.1007/s13577-024-01169-5.
This research delves into Primary Hyperoxaluria Type 2 (PH2), an autosomal recessive disorder precipitated by a unique case of compound heterozygous deleterious mutations in the GRHPR gene, specifically the intron2/3 c.214-2 T > G and the exon8 c.864-865delTG, leading to a premature stop codon at p.Val289fsTer22. The intron 2/3 variant (c.214-2 T > G) is a novel finding and is reported for the first time. These mutations are associated with profound alterations in protein structure and function. Employing patient-derived induced pluripotent stem cells (iPSCs), we have successfully generated a patient-specific model that exhibits the hallmarks of pluripotency, including typical stem cell morphology, expression of pluripotency markers, and a normal karyotype. The iPSCs are capable of differentiating into all three germ layers, underscoring their potential for regenerative medicine. The established iPSC line offers a promising platform for drug screening and regenerative medicine approaches for PH2.
本研究深入探讨了2型原发性高草酸尿症（PH2），这是一种常染色体隐性疾病，由GRHPR基因中复合杂合有害突变的独特病例引发，具体为内含子2/3的c.214 - 2 T＞G和外显子8的c.864 - 865delTG，导致在p.Val289fsTer22处出现过早终止密码子。内含子2/3变体（c.214 - 2 T＞G）是一项新发现，首次被报道。这些突变与蛋白质结构和功能的深刻改变相关。利用患者来源的诱导多能干细胞（iPSC），我们成功构建了一个患者特异性模型，该模型展现了多能性的特征，包括典型的干细胞形态、多能性标志物的表达以及正常的核型。iPSC能够分化为所有三个胚层，突出了它们在再生医学中的潜力。所建立的iPSC系为PH2的药物筛选和再生医学方法提供了一个有前景的平台。
