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

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.

Genetic and Clinical Phenotypic Analysis of Familial Stapes Sclerosis Caused by a NOG Mutation

“…In the family reported here, both cysteine 184 and 230 were affected, resulting in stapes rigidity, hearing loss, and phalangeal dysfunction [16]. These ndings con rm that mutations with the same NOG coding sequence can lead to different phenotypes and inter-family variation [17][18][19][20][21][22][23][24][25] . This suggests that disease expression can be independent of the location and type of NOG mutation.NOG Mutation contains a variety of syndromes.…”

Genetic and clinical phenotypic analysis of familial stapes sclerosis caused by a NOG mutation

“…In the family reported here, both cysteine 184 and 230 were affected, resulting in stapes rigidity, hearing loss, and phalangeal dysfunction [16]. These ndings con rm that mutations with the same NOG coding sequence can lead to different phenotypes and inter-family variation [17][18][19][20][21][22][23][24][25]. This suggests that disease expression can be independent of the location and type of NOG mutation.…”

Genetic and clinical phenotypic analysis of familial stapes sclerosis caused by a NOG mutation

“…In the family reported here, both cysteine 184 and 230 were affected, resulting in stapes rigidity, hearing loss, and phalangeal dysfunction [24]. These ndings con rm that mutations with the same NOG coding sequence can lead to different phenotypes and inter-family variation [13][14][15][16][17][18]22,25,26]. This suggests that disease expression can be independent of the location and type of NOG mutation.…”

“…Nog mutation site and clinical phenotype analysis we searched literature database and PubMED data Library to nd out the relevant literature of nog gene mutation.Tab le 1 lists the nog mutation sites reported so far Clinical phenotype [13][14][15][16][17][18][19]. The results showed that the mutation site of nog was varied, the clinical features also vary.…”