title: Mutations of MYH14 are associated to anorectal malformations with recto-perineal fistulas in a small subset of Chinese population.
abstract: BACKGROUND
  Anorectal malformations (ARMs) are among the most commonly congenital abnormalities of distal hindgut development, ranging from anal stenosis to anal atresia with or without fistulas and persistent cloaca. The etiology remains elusive for most ARM cases and the majority of genetic studies on ARMs were based on a candidate gene approach.
  
  
  METHODS
  In all eight family members of a non-consanguineous Chinese family, we performed whole-exome sequencing. Subsequently, exome sequencing of MYH14 in 72 unrelated probands with ARMs was performed. The accurate distribution of non-muscle myosin II heavy chain (NMHC II) was investigated by immunohistochemistry in serial sagittal sections of E11.5-13.5 mouse cloacal regions.
  
  
  RESULTS
  A homozygous mutation in MYH14 was identified in the two siblings of family 1. Compound heterozygous MYH14 changes were identified in an unrelated individual. Immunohistochemical analysis suggest stronger NMHC IIC localization in the epithelium of the murine embryonic cloaca, urorectal septum and hindgut compared with another two NMHC II isoforms.
  
  
  CONCLUSIONS
  This is the first identification of mutations in MYH14 as a cause of ARMs. The stronger localization of NMHC IIC in E11.5-13.5 mouse cloacal regions further supports the role of MYH14 in anorectal development.
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.|Department of Pediatric Surgery, Children's Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Zhongxian
authors.identifier: http://orcid.org/0000-0003-3379-9827
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.|Department of Pediatric Surgery, Children's Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Peng
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.|Department of Pediatric Surgery, Children's Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Guanglin
authors.initials: G
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.|Department of Pediatric Surgery, Children's Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.|Department of Pediatric Surgery, Children's Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Ziyang
authors.initials: Z
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.|Department of Pediatric Surgery, Children's Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Chunxia
authors.initials: C
authors.lastname: Du
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.|Department of Pediatric Surgery, Children's Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Rujin
authors.initials: R
authors.lastname: Zang
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.|Key Laboratory of Modern Toxicology (Nanjing Medical University), Ministry of Education, Nanjing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Su
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.|Department of Pediatric Surgery, Children's Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.|Department of Pediatric Surgery, Children's Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Hongxing
authors.initials: H
authors.lastname: Li
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.|Key Laboratory of Modern Toxicology (Nanjing Medical University), Ministry of Education, Nanjing, China.
authors.forename: Yankai
authors.initials: Y
authors.lastname: Xia
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.|Department of Pediatric Surgery, Children's Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Weibing
authors.identifier: http://orcid.org/0000-0002-3582-3408
authors.initials: W
authors.lastname: Tang
mesh_terms: D000818:Animals; D000071056:Anorectal Malformations / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D002988:Cloaca / Q000473:pathology; D005190:Family; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008813:Mice, Inbred ICR; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics*; D018995:Myosin Heavy Chains / Q000235:genetics*; D024462:Myosin Type II / Q000235:genetics*; D010375:Pedigree; D010502:Perineum / Q000000981:diagnostic imaging / Q000473:pathology*; D012003:Rectal Fistula / Q000000981:diagnostic imaging / Q000235:genetics*; D000073359:Exome Sequencing
chemical_list: D018995:Myosin Heavy Chains; D024462:Myosin Type II; C477830:MYH7b protein, human
keywords: 
  IHC; 
  MYH14; anorectal malformations; exome sequencing; mutations