Further delineation of facioaudiosymphalangism syndrome: Description of a family with a novel NOG mutation and without hearing loss

Abstract

Mutations in the NOG gene give rise to a wide range of clinical phenotypes. Noggin, the protein encoded by this gene is a secreted modulator of multiple pathways involved in both bone and joint development. Proximal symphalangism is commonly observed in patients bearing mutations in this gene, however secondary symptomes are often found including typical facies with hemicylindrical nose with bulbous tip, hyperopia, reduced mobility of multiple joints, hearing loss due to stapes fixation, and recurrent pain from affected joints. With large variation of the phenotype both within and between affected families careful delineation of the genotype-phenotype correlation is needed. In this work we describe a Danish family suffering from SYNS1 due to a novel NOG gene mutation (C230Y). We provide detailed clinical description of the family members presenting rare phenotype of the shoulders shared by affected individuals but no hearing loss, further adding to the phenotypic variability of the syndrome. With these findings we broaden the understanding of NOG-related-symphalangism spectrum disorder. © 2016 Wiley Periodicals, Inc.

Autosomal dominant stapes fixation, syndactyly, and symphalangism in a family with NOG mutation: Long term follow-up on surgical treatment

“…The affection was seen through more than four meiosis (family members of three generations), which may also confirm the pathogenicity. Substitution of Cysteine with tyrosine at position 230 has previously been reported as pathogenic [31] but in this study, we found a deletion and not a substitution. Bayat et al presented the novel mutation in NOG resulting in substitution of Cysteine 230 in a Danish family, but none of the affected family members had hearing loss [31].…”

“…Substitution of Cysteine with tyrosine at position 230 has previously been reported as pathogenic [31] but in this study, we found a deletion and not a substitution. Bayat et al presented the novel mutation in NOG resulting in substitution of Cysteine 230 in a Danish family, but none of the affected family members had hearing loss [31]. Another study reported a mutation in Cysteine 184 causing proximal symphalangism without hearing impairment [6].…”

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

“…Therefore, it is di cult to determine the relationship between the mutations and clinical phenotype. Bayat et al proposed a new mutation in NOG in which cysteine 230 was replaced in a Danish family, but none of the affected family members suffered hearing loss [15]. Another study reported that mutations in cysteine 184 caused no indication of hearing impairment.…”

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

“…Therefore, it is di cult to determine the relationship between the mutations and clinical phenotype. Bayat et al proposed a new mutation in NOG in a Danish family in which cysteine 230 was replaced, but none of the affected family members suffered hearing loss [23]. Another study reported that mutations in cysteine 184 caused no indication of hearing impairment.…”