...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>BMC Medical Genomics >Deletion of 2 amino acids in IHH in a Japanese family with brachydactyly type A1
【24h】

Deletion of 2 amino acids in IHH in a Japanese family with brachydactyly type A1

机译：用Brachydacty类型A1删除IHH中的2个氨基酸

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Brachydactyly type A1 (BDA1) is an autosomal dominant disorder characterized by uniform shortening of the middle phalanges in all digits. It is associated with variants in the Indian Hedgehog (IHH) gene, which plays a key role in endochondral ossification. To date, heterozygous pathogenic IHH variants involving several codons, which are restricted to a specific region of the N-terminal active fragment of IHH, have been reported. The purpose of this study was to identify the pathogenic variant in a Japanese family with BDA1 and to evaluate its pathogenesis with regard to previous reports. The proband, a 9-year-old boy, his siblings, and his father had shortened digits and a short stature of variable severity. Based on physical examinations, radiographic findings and family history, they were diagnosed with BDA1. This family is the first case of an isolated malformation in Japan. Sanger sequencing of IHH was performed on these individuals and on the proband’s unaffected mother. The significance of the variants was assessed using three-dimensional analysis methods. Sanger sequencing showed a novel IHH heterozygous variant, NM_002181.4:c.544_549delTCAAAG(p.Ser182Lys183del) [NC_000002.12:g.219057461_219057466del].. These two residues are located outside the cluster region considered a hotspot of pathogenic variants. Three-dimensional modelling showed that S182 and K183 are located on the same surface as other residues associated with BDA1. Analysis of residue interactions across the interface between IHH and its interacting receptor protein revealed the presence of hydrogen bonds between them. We report a novel variant, NM_002181.4:c.544_549delTCAAAG (p.Ser182Lys183del) [NC_000002.12:g.219057461_219057466del] in a Japanese family with BDA1. Indeed, neither variations in codons 182 or 183 nor with such two-amino-acid deletions in IHH have been reported previously. Although these two residues are located outside the cluster region considered a hotspot of pathogenic variants, we speculate that this variant causes BDA1 through impaired interactions between IHH and target receptor proteins in the same manner as other pathogenic variants located in the cluster region. This report expands the genetic spectrum of BDA1.
机译：Brachydactyly类型A1（BDA1）是一种常染色体显性障碍，其特征，其特征在于所有数字中的中间阵容均匀缩短。它与印度刺猬（IHH）基因的变体有关，该基因在Contochondross骨化中发挥着关键作用。迄今为止，已经报道了涉及几个密码子的杂合性致病性IHH变体，其限于IHH的N-末端活性片段的特定区域。本研究的目的是鉴定日本家庭中的致病变异，并评估其关于先前报告的发病机制。一位一年，一个9岁的男孩，他的兄弟姐妹，他的父亲缩短了数字和矮小的可变严重程度。基于体检，放射线摄影结果和家族史，他们被诊断为BDA1。这个家庭是日本第一种孤立畸形的案例。 IHH的Sanger测序是对这些个人进行的，并在证据不受影响的母亲上进行。使用三维分析方法评估变体的重要性。 Sanger测序显示新型IHH杂合子变体，NM_002181.4：C.544_549DeltcaAG（P.SER182LYS183DEL）[NC_000002.12：G.219057461_219057466DEL]。这两个残基位于簇区外，被认为是致病变异的热点。三维建模显示S182和K183位于与与BDA1相关的其他残基相同的表面上。 IHH与其相互作用蛋白与其相互作用蛋白质之间的残基相互作用的分析显示它们之间的氢键存在。我们报告了一个新型VAR，NM_002181.4：C.544_549DELTCAAG（P.SER182LYS183DEL）[NC_000002.12：G.219057461_2190574661_2190574661_219057466DEL]在日本家庭中，具有BDA1。实际上，先前已经报道了密码子182或183中的变化也不是在IHH中的这种两氨基酸缺失。尽管这两个残留物位于簇区域之外，但是被认为是致病变体的热点，但是推测该变体通过IHH和靶受体蛋白之间的损伤相互作用以与位于簇区域中的其他致病变体相同的方式导致BDA1。本报告扩展了BDA1的遗传频谱。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号