title: Novel and reported APC germline mutations in Chinese patients with familial adenomatous polyposis.
abstract: OBJECTIVE
  Familial adenomatous polyposis (FAP) is mainly caused by germline mutations in the adenomatous polyposis coli (APC) gene. This study aimed to detect pathogenic variants in five Chinese FAP families and review all previously reported pathogenic variants of APC gene in Chinese population.
  
  
  METHODS
  Five non-consanguineous FAP families and 100 unrelated ethnicity-matched controls were included in the study. Sanger sequencing was performed to screen for APC coding and splicing variants. Chinese and English literature on APC germline mutations were reviewed to compile the mutation spectrum of APC gene in Chinese FAP patients.
  
  
  RESULTS
  One pathogenic variant was detected in each family for the five pedigrees we tested. Three variants (c.3183_3187delACAAA, c.2626C>T and c.1312+1G>A) were previously reported as pathogenic. The other two variants were novel: c.794_795insG/p.Val266SerfsTer11 and c.2142_2143insG/p.His715AlafsTer19. They are absent from public databases (1000 Genomes, dbSNP, ESP and ExAC) and 100 normal controls, and are classified as pathogenic based on the new ACMG/AMP variant classification guidelines. Literature review and current study revealed a total of 82 different pathogenic variants from 127 Chinese FAP families. Among these families, 83 families had frameshift variants (65.35%), 26 with nonsense variants (20.47%), six with splice site variants (4.72%), three with missense variants (2.36%) and nine with large deletion or duplication variants (7.09%). Apart from the two previously reported mutation hotspots c.3927_3931delAAAGA (20.47%) and c.3183_3187delACAAA (7.09%), c.847C>T/p.Arg283Ter variant occurred with a frequency of 3.15% (4 out of 127) in Chinese FAP patients.
  
  
  CONCLUSIONS
  We reported two novel pathogenic variants. The comprehensive compilation of variants and comparison revealed largely similar mutation spectrum between Chinese and Western patient populations. Some unique features noticed in Chinese patient population may help to better understand the pathogenesis of FAP.
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan 410078, China; Department of Genetic Metabolism, Children's Hospital, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530003, China.
authors.forename: Shujie
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Genetic Metabolism, Children's Hospital, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530003, China.
authors.forename: Haisong
authors.initials: H
authors.lastname: Qin
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan 410078, China.
authors.forename: Weigang
authors.initials: W
authors.lastname: Lv
authors.affiliation: Department of Genetic Metabolism, Children's Hospital, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530003, China.
authors.forename: Shiyu
authors.initials: S
authors.lastname: Luo
authors.affiliation: Department of Genetic Metabolism, Children's Hospital, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530003, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Genetic Metabolism, Children's Hospital, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530003, China.
authors.forename: Chunyun
authors.initials: C
authors.lastname: Fu
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan 410078, China.
authors.forename: Ruiyu
authors.initials: R
authors.lastname: Ma
authors.affiliation: Department of Genetic Metabolism, Children's Hospital, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530003, China.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Genetic Metabolism, Children's Hospital, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530003, China. Electronic address: chenshaoke123@163.com.
authors.forename: Shaoke
authors.initials: S
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan 410078, China. Electronic address: wulingqian@sklmg.edu.cn.
authors.forename: Lingqian
authors.initials: L
authors.lastname: Wu
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics*; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide
chemical_list: C555337:APC protein, human; D025601:Adenomatous Polyposis Coli Protein
keywords: Adenomatous polyposis coli; Chinese; FAP; Germline mutation; Novel variant