| 摘要: |
| ［摘要］ 目的 分析一个罕见的镫骨强直伴拇指（趾）宽大综合征(SABTT)家系（编号HuB-341）的临床及遗传学特征，应用新一代高通量测序鉴定其致病基因。方法 对该家系成员进行病史调查、体格检查、影像学检查以及听力学检查，绘制家系图谱。同时抽取家系成员外周静脉血并提取DNA，对先证者进行全外显子组测序，对候选基因通过Sanger测序进行家系验证，明确该家系的致病基因。结果 HuB-341家系来自湖北省武汉市，2代3人。先证者为家系唯一耳聋患者，临床表现为双耳传导性聋并伴有特征性面容、拇趾宽大、弱视及远视。对先证者进行全外显子组测序鉴定了NOG基因一个新的突变位点，即c.679G>T，引起编码第227位的谷氨酸突变为终止密码子（p.Glu227Ter）。家系验证提示该突变为新生突变。该突变在多物种间是保守的。结论 该家系临床诊断为SABTT，通过先证者全外显子组测序及家系验证，鉴定了NOG基因一个新的突变位点，即c.679G>T（p.Glu227Ter）。该突变为家系的致病突变，临床诊断和分子诊断相结合提高了对该罕见病的认识，为该家系的遗传咨询提供了科学依据。 |
| 关键词: 镫骨强直伴拇指（趾）宽大综合征 NOG基因 传导性聋 突变 |
| DOI：10.3969/j.issn.1674-3806.2023.05.02 |
| 分类号:R 764.43 |
| 基金项目:国家自然科学基金项目（编号：81200749）；湖北省自然科学基金面上项目（编号：2018CFB719）；湖北省卫生健康委联合基金项目（编号：WJ2018H0081）；湖北省卫生健康委基金项目（编号：WJ2023M089） |
|
| Identification of a novel NOG gene mutation in a pedigree having stapes ankylosis with broad thumbs and toes and analysis of the clinical manifestations |
|
ZAHNG Zhao, LU Yu, YANG Chang-liang, et al.
|
|
Department of Otorhinolaryngology Head and Neck Surgery, General Hospital of Central Theater Command, Wuhan 430070, China
|
| Abstract: |
| ［Abstract］ Objective To analyze the clinical and genetic characteristics of a rare pedigree(No. HuB-341) having stapes ankylosis with broad thumbs and toes(SABTT) and to identify the disease-causing genes using the next-generation sequencing technology. Methods The medical history investigation, physical examination, imaging examination and audiological examination of the family members were performed. The pedigree of the family was drawn. At the same time, the peripheral venous blood of the family members was collected and their deoxyribonucleic acids(DNAs) were extracted. Whole exome sequencing was conducted on the proband, and family verification was conducted on candidate genes by Sanger sequencing technology to identify the disease-causing genes in this pedigree. Results The HuB-341 pedigree came from Wuhan, Hubei Province, and consisted of 3 persons in 2 generations. The proband was the only deaf patient in her family. She showed bilateral conductive hearing loss accompanied by characteristic facial features, broad toes, amblyopia and hyperopia. Whole exome sequencing was performed on the proband and a novel mutation in the NOG gene was identified, that is, c.679G>T, which caused the mutation of glutamic acid coding 227th position to be a stop codon(p.Glu227Ter). The results of the family verification indicated that the mutation was a novel mutation, which was conservative among multiple species. Conclusion The pedigree is clinically diagnosed as SABTT. A novel mutation of the NOG gene, c.679G>T(p.Glu227Ter), is identified through the whole exome sequencing and family validation of the proband. The mutation is a pathogenic mutation of the pedigree. The combination of clinical diagnosis and molecular diagnosis improves the understanding of this rare disease and provides scientific basis for genetic counseling of the pedigree. |
| Key words: Stapes ankylosis with broad thumbs and toes(SABTT) NOG gene Conductive hearing loss Mutation |
