Ishino Takashi, Takeno Sachio, Hirakawa Katsuhiro
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.
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.
Eur J Med Genet. 2015 Sep;58(9):427-32. doi: 10.1016/j.ejmg.2015.06.005. Epub 2015 Jul 26.
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.
人类头蛋白（NOG）基因突变会导致多种骨骼疾病，表现为镫骨强直并伴有宽拇指和宽脚趾（SABTT）、近端指间关节融合（SYM1）、多关节融合综合征1（SYNS1）、跗腕骨联合综合征（TCC）和B2型短指症（BDB2）。这些表型被定义为具有相同突变的NOG相关综合征。其中一些综合征以镫骨强直作为多种骨骼症状之一。在此，我们报告一个因先天性镫骨强直导致传导性听力损失的日本家族。这个家族表现出多种特征，被诊断为SABTT。我们通过直接测序分析对该家族的NOG进行了分析，发现了一种新的NOG突变：c.682 T>G（p.C228G）。我们的结果以及对先前NOG蛋白构象病例的回顾表明，这种突变的NOG蛋白导致骨形态发生蛋白（BMPs）拮抗剂活性发生变化和/或单倍体不足，这可能损害了第二指的结构。
