title: Mutation analysis of Chinese sporadic congenital sideroblastic anemia by targeted capture sequencing.
abstract: BACKGROUND
  Congenital sideroblastic anemias (CSAs) comprise a group of heterogenous genetic diseases that are caused by the mutation of various genes involved in heme biosynthesis, iron-sulfur cluster biogenesis, or mitochondrial solute transport or metabolism. However, approximately 40% of patients with CSA have not been found to have pathogenic gene mutations. In this study, we systematically analyzed the mutation profile in 10 Chinese patients with sporadic CSA.
  
  
  RESULTS
  We performed targeted deep sequencing analysis in ten patients with CSA using a panel of 417 genes that included known CSA-related genes. Mitochondrial genomes were analyzed using next-generation sequencing with a mitochondria enrichment kit and the HiSeq2000 sequencing platform. The results were confirmed by Sanger sequencing. The ALAS2 mutation was detected in one patient. SLC25A38 mutations were detected in three patients, including three novel mutations. Mitochondrial DNA deletions were detected in two patients. No disease-causing mutations were detected in four patients.
  
  
  CONCLUSIONS
  To our knowledge, the pyridoxine-effective mutation C471Y of ALAS2, the compound heterozygous mutation W87X, I143Pfs146X, and the homozygous mutation R134C of SLC25A38 were found for the first time. Our findings add to the number of reported cases of this rare disease and to the CSA pathogenic mutation database. Our findings expand the phenotypic profile of mitochondrial DNA deletion mutations. This work also demonstrates the application of a congenital blood disease assay and targeted capture sequencing for the genetic screening analysis and diagnosis of heterogenous genetic CSA.
authors.affiliation: Division of Pediatric Blood Diseases Center, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 288 Nanjing Road, Tianjin, 300020, People's Republic of China. annwenbin@163.com.
authors.forename: Wenbin
authors.initials: W
authors.lastname: An
authors.affiliation: Division of Pediatric Blood Diseases Center, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 288 Nanjing Road, Tianjin, 300020, People's Republic of China. jingliaozh@163.com.
authors.forename: Jingliao
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Division of Pediatric Blood Diseases Center, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 288 Nanjing Road, Tianjin, 300020, People's Republic of China. clx.886@163.com.
authors.forename: Lixian
authors.initials: L
authors.lastname: Chang
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 288 Nanjing Road, Tianjin, 300020, People's Republic of China. yczhang1983@126.com.
authors.forename: Yingchi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Division of Pediatric Blood Diseases Center, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 288 Nanjing Road, Tianjin, 300020, People's Republic of China. wanyang1988pumc@126.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wan
authors.affiliation: Division of Pediatric Blood Diseases Center, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 288 Nanjing Road, Tianjin, 300020, People's Republic of China. renyuanyuans@126.com.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Ren
authors.affiliation: MyGenostics Inc., Baltimore, MD, USA. ndy@mygeno.cn.
authors.forename: Deyun
authors.initials: D
authors.lastname: Niu
authors.affiliation: MyGenostics Inc., Baltimore, MD, USA. jw2231@mygeno.cn.
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.affiliation: Division of Pediatric Blood Diseases Center, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 288 Nanjing Road, Tianjin, 300020, People's Republic of China. xfzhu1981@126.com.|State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 288 Nanjing Road, Tianjin, 300020, People's Republic of China. xfzhu1981@126.com.
authors.forename: Xiaofan
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Division of Pediatric Blood Diseases Center, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 288 Nanjing Road, Tianjin, 300020, People's Republic of China. guoyanr@126.com.|State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 288 Nanjing Road, Tianjin, 300020, People's Republic of China. guoyanr@126.com.
authors.forename: Ye
authors.initials: Y
authors.lastname: Guo
mesh_terms: D000293:Adolescent; D000756:Anemia, Sideroblastic / Q000235:genetics*; D044466:Asian People; D002675:Child, Preschool; D004252:DNA Mutational Analysis / Q000379:methods*; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008967:Molecular Biology / Q000379:methods*; D009154:Mutation