A Novel Missense Mutation of NOG Interferes With the Dimerization of NOG and Causes Proximal Symphalangism Syndrome in a Chinese Family

Xiuhong Pang; Zhaoyan Wang; Yongchuan Chai; Hongsai Chen; Lei Li; Lianhua Sun; Huan Jia; Hao Wu; Tao Yang

doi:10.1177/0003489415582257

A Novel Missense Mutation of NOG Interferes With the Dimerization of NOG and Causes Proximal Symphalangism Syndrome in a Chinese Family

Ann Otol Rhinol Laryngol. 2015 Sep;124(9):745-51. doi: 10.1177/0003489415582257. Epub 2015 Apr 17.

Authors

Xiuhong Pang¹, Zhaoyan Wang², Yongchuan Chai², Hongsai Chen², Lei Li², Lianhua Sun², Huan Jia², Hao Wu², Tao Yang³

Affiliations

¹ 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.
² 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.
³ 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.

PMID: 25888563
DOI: 10.1177/0003489415582257

Abstract

Objectives: 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.

Keywords: NOG; conductive hearing impairment; dimerization; mutation; proximal symphalangism.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acoustic Impedance Tests / methods
Bone Morphogenetic Proteins / genetics
Brachydactyly* / diagnosis
Brachydactyly* / genetics
Brachydactyly* / physiopathology
Brachydactyly* / surgery
Carrier Proteins / genetics*
China
Foot Deformities, Congenital* / diagnostic imaging
Foot Deformities, Congenital* / genetics
Hand Deformities, Congenital* / diagnostic imaging
Hand Deformities, Congenital* / genetics
Hearing Loss, Conductive* / genetics
Hearing Loss, Conductive* / surgery
Humans
Male
Mutation, Missense
Pedigree
Protein Multimerization / physiology*
Radiography
Stapes Surgery / methods

Substances

Bone Morphogenetic Proteins
Carrier Proteins
noggin protein

Supplementary concepts

Sillence syndrome