Abstract：
The neurometabolic disorder known as biotin-thiamine-responsive basal ganglia disease (BTBGD) is a rare autosomal recessive condition linked to bi-allelic pathogenic mutations in the SLC19A3 gene. BTBGD is characterized by progressive encephalopathy, confusion, seizures, dysarthria, dystonia, and severe disabilities. Diagnosis is difficult due to the disease\'s rare nature and diverse clinical characteristics. The primary treatment for BTBGD at this time is thiamine and biotin supplementation, while its long-term effectiveness is still being investigated. In this study, we have generated two clones of induced pluripotent stem cells (iPSCs) from a 10-year-old female BTBGD patient carrying a homozygous mutation for the pathogenic variant in exon 5 of the SLC19A3 gene, c.1264A > G (p.Thr422Ala). We have confirmed the pluripotency of the generated iPS lines and successfully differentiated them to neural progenitors. Because our understanding of genotype-phenotype correlations in BTBGD is limited, the establishment of BTBGD-iPSC lines with a homozygous SLC19A3 mutation provides a valuable cellular model to explore the molecular mechanisms underlying SLC19A3-associated cellular dysfunction. This model holds potential for advancing the development of novel therapeutic strategies.
摘要：
称为生物素-硫胺素反应性基底神经节病（BTBGD）的神经代谢紊乱是一种罕见的常染色体隐性遗传病，与SLC19A3基因的双等位基因致病突变有关。BTBGD的特点是进行性脑病，混乱,癫痫发作,构音障碍,肌张力障碍,严重残疾。由于该病的罕见性质和不同的临床特征，诊断困难。此时BTBGD的主要治疗方法是补充硫胺素和生物素，而其长期有效性仍在调查中。在这项研究中,我们已经从一名10岁的女性BTBGD患者中产生了两个诱导多能干细胞（iPSCs）克隆，该患者携带SLC19A3基因外显子5的致病变异的纯合突变，c.1264A>G（p。Thr422Ala）。我们已经证实了所产生的iPS系的多能性,并成功地将它们分化为神经祖细胞。因为我们对BTBGD中基因型-表型相关性的理解是有限的，具有纯合SLC19A3突变的BTBGD-iPSC系的建立为探索SLC19A3相关细胞功能障碍的分子机制提供了有价值的细胞模型.该模型具有促进新型治疗策略发展的潜力。
