title: Novel NOG mutation in Japanese patients with stapes ankylosis with broad thumbs and toes.
abstract: Human noggin (NOG) gene mutation causes multiple bony disorders showing up as stapes ankylosis with broad thumbs and toes (SABTT), proximal symphalangism (SYM1), multiple synostoses syndrome 1 (SYNS1), tarsal-carpal coalition syndrome (TCC) and brachydactyly type B2 (BDB2). These phenotypes are defined as NOG-related syndromes with the same mutation. Some of these syndromes feature stapes ankylosis as one of the several bony symptoms. Here, we report a Japanese family with conductive hearing loss due to congenital stapes ankylosis. This family showed multiple features and was diagnosed with SABTT. We performed analysis of the NOG in the family by direct sequence analysis, and found a novel NOG mutation: c.682 T> G (p.C228G). Our results and a review of previous cases with NOG protein conformation suggest that this mutated NOG protein lead to a change in antagonist activity in BMPs and/or a haploinsufficiency that likely impaired finger 2 structure.
authors.affiliation: Department of Otorhinolaryngology, Head & Neck Surgery, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima City, Hiroshima 734-8551, Japan. Electronic address: takashiishino@hotmail.com.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ishino
authors.affiliation: Department of Otorhinolaryngology, Head & Neck Surgery, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima City, Hiroshima 734-8551, Japan.
authors.forename: Sachio
authors.initials: S
authors.lastname: Takeno
authors.affiliation: Department of Otorhinolaryngology, Head & Neck Surgery, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima City, Hiroshima 734-8551, Japan.
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Hirakawa
mesh_terms: D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D002348:Carpal Bones / Q000002:abnormalities*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005532:Foot Deformities, Congenital / Q000175:diagnosis / Q000235:genetics*; D056726:Genetic Association Studies; D006228:Hand Deformities, Congenital / Q000175:diagnosis / Q000235:genetics*; D057895:Haploinsufficiency / Q000235:genetics; D006314:Hearing Loss, Conductive / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011487:Protein Conformation; D013199:Stapes / Q000002:abnormalities*; D013580:Synostosis / Q000175:diagnosis / Q000235:genetics*; D013639:Tarsal Bones / Q000002:abnormalities*; D013933:Thumb / Q000002:abnormalities; D014034:Toes / Q000002:abnormalities; D000099176:Noggin Protein
chemical_list: D002352:Carrier Proteins; D000099176:Noggin Protein
keywords: Conformation; Mutation; NOG; Phenotype; SABTT; SYNS1; p.C228G