PDF(Pubmed)
Abstract：
It is known that a nevoid basal cell carcinoma syndrome (NBCCS) is characterized by a combination of developmental abnormalities and a predisposition to form various tumors. Although it is possible to create disease models via gene editing, there are significant potential problems with this approach such as off-target mutations and differences in SNPs. On the other hand, since disease families share common SNPs, research using iPSCs derived from both patients and healthy siblings of the same disease family is very important. Thus, establishment of induced pluripotent stem cells derived from patients and healthy siblings of the same NBCCS family will be of great importance to study the etiology of this disease and to develop therapeutics. In this study, we generated hiPSCs using peripheral blood mononuclear cells derived from the patients and healthy siblings of familial NBCCS with the novel mutation in PTCH1_c.3298_3299insAAG in the feeder- and serum-free culture conditions using SeVdp. In addition, disease-specific hiPSCs such as those expressing the PTCH1_c.3298_3299insAAG mutation could be powerful tools for revealing the genotype-phenotype relationship and pathogenicity of NBCCS.
摘要：
已知的是,结节状基底细胞癌综合征(NBCCS)的特征在于发育异常和形成各种肿瘤的倾向的组合。尽管可以通过基因编辑创建疾病模型，这种方法存在显著的潜在问题,例如脱靶突变和SNP差异.另一方面,因为疾病家族有共同的SNP，使用来自同一疾病家族的患者和健康兄弟姐妹的iPSCs进行研究非常重要。因此，建立来自相同NBCCS家族的患者和健康同胞的诱导多能干细胞对于研究这种疾病的病因和开发治疗方法非常重要。在这项研究中,我们使用来自患者和家族性NBCCS健康同胞的外周血单核细胞,在无Feeder和无血清培养条件下,使用SeVdp,在PTCH1_c.3298_3299insAAG中具有新突变,产生了hiPSCs.此外,疾病特异性hiPSCs，例如表达PTCH1_c.3298_3299insAAG突变的hiPSCs可能是揭示NBCCS基因型-表型关系和致病性的有力工具。
