title: A novel nonsense mutation in the NOG gene causes familial NOG-related symphalangism spectrum disorder.
abstract: The human noggin (NOG) gene is responsible for a broad spectrum of clinical manifestations of NOG-related symphalangism spectrum disorder (NOG-SSD), which include proximal symphalangism, multiple synostoses, stapes ankylosis with broad thumbs (SABTT), tarsal-carpal coalition syndrome, and brachydactyly type B2. Some of these disorders exhibit phenotypes associated with congenital stapes ankylosis. In the present study, we describe a Japanese pedigree with dactylosymphysis and conductive hearing loss due to congenital stapes ankylosis. The range of motion in her elbow joint was also restricted. The family showed multiple clinical features and was diagnosed with SABTT. Sanger sequencing analysis of the NOG gene in the family members revealed a novel heterozygous nonsense mutation (c.397A>T; p.K133*). In the family, the prevalence of dactylosymphysis and hyperopia was 100% while that of stapes ankylosis was less than 100%. Stapes surgery using a CO2 laser led to a significant improvement of the conductive hearing loss. This novel mutation expands our understanding of NOG-SSD from clinical and genetic perspectives.
authors: Department of Otolaryngology, Sapporo Medical University School of Medicine , Sapporo, Japan.
authors: Kenichi
authors: K
authors: Takano
authors: Department of Otolaryngology, Sapporo Medical University School of Medicine, Sapporo, Japan; Department of Medical Genetics, Liberal Arts and Science, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Noriko
authors: N
authors: Ogasawara
authors: Department of Integrated Sciences in Physics and Biology, College of Humanities and Sciences, Nihon University , Tokyo, Japan.
authors: Tatsuo
authors: T
authors: Matsunaga
authors: Department of Integrated Sciences in Physics and Biology, College of Humanities and Sciences, Nihon University , Tokyo, Japan.
authors: Hideki
authors: H
authors: Mutai
authors: Department of Medical Genetics, Liberal Arts and Science, Sapporo Medical University School of Medicine , Sapporo, Japan.
authors: Akihiro
authors: A
authors: Sakurai
authors: Department of Medical Genetics, Liberal Arts and Science, Sapporo Medical University School of Medicine , Sapporo, Japan.
authors: Aki
authors: A
authors: Ishikawa
authors: Department of Otolaryngology, Sapporo Medical University School of Medicine , Sapporo, Japan.
authors: Tetsuo
authors: T
authors: Himi