title: A Novel Missense Mutation of NOG Interferes With the Dimerization of NOG and Causes Proximal Symphalangism Syndrome in a Chinese Family.
abstract: OBJECTIVE
  NOG is an antagonist to bone morphogenetic proteins and plays an important role in proper bone and joint development. Dominant mutations in NOG may lead to a series of symphalangism spectrum disorders. In this study, we aimed to identify the genetic cause and the pathogenic mechanism of an autosomal dominant disorder with cosegregating proximal symphalangism and conductive hearing impairment in a Chinese family.
  
  
  METHODS
  Mutation screening of NOG was performed in the affected family members by polymerase chain reaction (PCR) amplification and direct sequencing. Western blotting analysis of NOG was performed in the leukocyte samples of the family members.
  
  
  RESULTS
  A novel p.W150C heterozygous mutation in NOG was identified cosegregating with the proximal symphalangism disorder in the family. Western blotting analysis showed that the p.W150C mutation interferes with the dimerization of the mutant NOG.
  
  
  CONCLUSIONS
  Our results agreed with previously published results of in vitro studies and suggested that impaired dimerization of mutant NOG is an important pathogenic mechanism for the NOG-related symphalangism spectrum disorder.
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China Ear Institute, Shanghai Jiaotong University, Shanghai, China Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China Department of Otorhinolaryngology-Head and Neck Surgery, Yangzhou University Medical College, Jiangsu Province, China.
authors.forename: Xiuhong
authors.initials: X
authors.lastname: Pang
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China Ear Institute, Shanghai Jiaotong University, Shanghai, China Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China.
authors.forename: Zhaoyan
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China Ear Institute, Shanghai Jiaotong University, Shanghai, China Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China.
authors.forename: Yongchuan
authors.initials: Y
authors.lastname: Chai
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China Ear Institute, Shanghai Jiaotong University, Shanghai, China Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China.
authors.forename: Hongsai
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China Ear Institute, Shanghai Jiaotong University, Shanghai, China Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China Ear Institute, Shanghai Jiaotong University, Shanghai, China Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China.
authors.forename: Lianhua
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China Ear Institute, Shanghai Jiaotong University, Shanghai, China Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Jia
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China Ear Institute, Shanghai Jiaotong University, Shanghai, China Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China Ear Institute, Shanghai Jiaotong University, Shanghai, China Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China yangtfxl@sina.com wuhao622@sina.cn.
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
mesh_terms: D000158:Acoustic Impedance Tests / Q000379:methods; D019485:Bone Morphogenetic Proteins / Q000235:genetics; D059327:Brachydactyly / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology / Q000601:surgery; D002352:Carrier Proteins / Q000235:genetics*; D002681:China; D005532:Foot Deformities, Congenital / Q000000981:diagnostic imaging / Q000235:genetics; D006228:Hand Deformities, Congenital / Q000000981:diagnostic imaging / Q000235:genetics; D006314:Hearing Loss, Conductive / Q000235:genetics / Q000601:surgery; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D055503:Protein Multimerization / Q000502:physiology*; D011859:Radiography; D013201:Stapes Surgery / Q000379:methods; D000099176:Noggin Protein
chemical_list: D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D000099176:Noggin Protein
keywords: NOG; conductive hearing impairment; dimerization; mutation; proximal symphalangism