講演情報
[OE9-3]MELAS患者におけるシングルセルレベルでのミトコンドリアDNAヘテロプラスミー測定の有用性
○岡崎 敦子1, 新田 和広1,2, 八塚 由紀子1, 杉浦 歩1, 荒尾 正人3, 志村 優4, 海老原 知博4, 小貫 孝則4, 市本 景子4, 大竹 明3,5,6, 村山 圭4, 岡崎 康司1,2 (1.順天堂大学 大学院医学研究科 難治性疾患診断・治療学, 2.理化学研究所 生命医科学研究センター 応用ゲノム解析技術研究チーム, 3.埼玉医科大学 小児科, 4.千葉県こども病院 代謝科, 5.埼玉医科大学病院 難病センター, 6.埼玉医科大学 ゲノム医療科)
【Background】 Mitochondrial DNA heteroplasmy has mainly been assessed with bulk sequencing in patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome. However, heteroplasmy distributions at the single-cell level in patients with MELAS, together with detailed clinical and biochemical information, has yet to be explored.【Methods】 We used the mitochondrial DNA single-cell assay for transposase-accessible chromatin sequencing method on skin fibroblasts obtained from six patients with MELAS of differing severity and heteroplasmy, as assessed by bulk sequencing. 【Results】 Different heteroplasmy distributions at the single-cell level were identified in skin fibroblasts from all six patients. Four patients with different outcomes showed similar bulk heteroplasmy rates with normal mitochondrial respiratory chain (MRC) enzyme activities, while the single-cell heteroplasmy distribution patterns differed between the patients.
【Conclusion】 Our results suggest the importance of measuring the heteroplasmy of causative mitochondrial DNA variants at the single-cell level in patients with MELAS. Take-home message: Measuring heteroplasmy of causative mitochondrial DNA variants at the single-cell level could be useful in patients with MELAS.
【Conclusion】 Our results suggest the importance of measuring the heteroplasmy of causative mitochondrial DNA variants at the single-cell level in patients with MELAS. Take-home message: Measuring heteroplasmy of causative mitochondrial DNA variants at the single-cell level could be useful in patients with MELAS.