dentification of mutations in patients with acquired pure red cell aplasia  

作　　者：Xinchao Zhang Yi Shi Lingjun Song Chang Shen Qi Cai Zhou Zhang Jun Wu Guohui FU Weiwei Shen 

机构地区：[1]Pathology Center, Shanghai General Hospital/Faculty of Medicine, Shanghai 200025, China [2]Key Laboratory of Basic Medicine, Shanghai Jiao Tong University School of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China [3]Key Laboratory of Systems Biomedicine (Ministry of Education) and Collaborative Innovation Center of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China [4]Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China [5]Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China [6]Burning Rock Biotech, Shanghai 201100, China

出　　处：《Acta Biochimica et Biophysica Sinica》2018年第7期685-692,共8页生物化学与生物物理学报（英文版）

基　　金：This work was supported by the grants from the National Natural Science Foundation of China （Nos. 81372637 and 81502423）, the National Key Technology R＆D Program of China （No. 2014BAI0 9B03）, the Key Projects in Shanghai Science ＆ Technology Pillar Program for Biomedicine （No. 14431904700） and Shanghai Pujiang Program （No. 16PJ1405300）.

摘　　要：Idiopathic acquired pure red cell aplasia （PRCA） is a rare, autoimmune-related disease. This study aimed to describe the previously unidentified DNA alterations associated with PRCA. Here, next generation sequencing using a panel containing 295 critical genes was applied to detect potentially pathogenic mutations in four patients with PRCA. A total of 529 mutations were identified and further classified into three categories, namely, uncertain （n = 25）, likely benign （n = 20） and benign （n = 484） mutations, based on the American College of Medical Genetics and Genomics （ACMG） 2015 guidelines and ClinVar database. The spatial proximity between two loci of the uncertain or benign mutations was evaluated using Hi-C datasets of KBM7 and K562 cell lines, respectively. Significant spatial proximity was observed in uncertain mutation pairs compared with benign mutation pairs. In addition, 17 variants were eventually identified after excluding those with mutant frequencies 〉0,001, including 7 newly identified variants. FANCF and LRP1B mutations existed twice in patients. FANCF and LRP1B mutations were likely to affect protein sta- bility based on prediction analysis. Taken together, our data may provide valuable information about PRCA. FANCF and LRP1B mutations may be associated with acquired PRCA.Idiopathic acquired pure red cell aplasia （PRCA） is a rare, autoimmune-related disease. This study aimed to describe the previously unidentified DNA alterations associated with PRCA. Here, next generation sequencing using a panel containing 295 critical genes was applied to detect potentially pathogenic mutations in four patients with PRCA. A total of 529 mutations were identified and further classified into three categories, namely, uncertain （n = 25）, likely benign （n = 20） and benign （n = 484） mutations, based on the American College of Medical Genetics and Genomics （ACMG） 2015 guidelines and ClinVar database. The spatial proximity between two loci of the uncertain or benign mutations was evaluated using Hi-C datasets of KBM7 and K562 cell lines, respectively. Significant spatial proximity was observed in uncertain mutation pairs compared with benign mutation pairs. In addition, 17 variants were eventually identified after excluding those with mutant frequencies 〉0,001, including 7 newly identified variants. FANCF and LRP1B mutations existed twice in patients. FANCF and LRP1B mutations were likely to affect protein sta- bility based on prediction analysis. Taken together, our data may provide valuable information about PRCA. FANCF and LRP1B mutations may be associated with acquired PRCA.

关 键 词：PRCA DNA alteration spatial proximity FANCF LRP1B 

分 类 号：S831.5[农业科学—畜牧学] TU831.7[农业科学—畜牧兽医]