Jiao Kexin, Zhang Jialong, Wang Ningning, Gu Xingyu, Chang Xuechun, Xia Xingyu, Zhu Bochen, Gao Mingshi, Cheng Nachuan, Zhao Chongbo, Xi Jianying, Zhu Wenhua
Department of Neurology, Huashan Hospital Fudan University, No.12 Middle Wulumuqi Road, Shanghai, China; National Center for Neurological Disorders (NCND), Shanghai, China; Huashan Rare Disease Center, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Department of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, MI 55455, USA.
Stem Cell Res. 2024 Dec;81:103562. doi: 10.1016/j.scr.2024.103562. Epub 2024 Sep 14.
GlcNAc2-epimerase myopathy is a rare autosomal recessive myopathy characterized by distal involvement in the lower extremities. Our study reprogrammed human-induced pluripotent stem cells from peripheral blood mononuclear cells of a patient with GNE gene deep intronic variant c.862 + 870C>T and c.478C>T compound heterozygous mutations that co-segregated with the disease. The generated iPSCs express pluripotent cell markers with no mycoplasma contamination. Additionally, these iPSCs demonstrated pluripotency, the capacity to differentiate into the three germ layers, and maintained normal karyotypes. Importantly, we identified that these iPSCs possess the same specific mutations as the patient, making them a robust model for studying GNE myopathy and developing potential therapeutic interventions.
N-乙酰葡糖胺-2-表异构酶肌病是一种罕见的常染色体隐性肌病，其特征是下肢远端受累。我们的研究从一名患有GNE基因内含子深处变体c.862 + 870C>T和c.478C>T复合杂合突变且该突变与疾病共分离的患者的外周血单核细胞中重编程了人诱导多能干细胞。所产生的诱导多能干细胞表达多能细胞标志物且无支原体污染。此外，这些诱导多能干细胞表现出多能性、分化为三个胚层的能力，并维持正常核型。重要的是，我们确定这些诱导多能干细胞具有与患者相同的特定突变，使其成为研究GNE肌病和开发潜在治疗干预措施的有力模型。
