Li Xia, Zhao Shengbo, Bi Xianyun, Lou Fan, Zeng Wenjuan, Gao Yan, Mao Zhiyong, Ma Jing
Department of Otolaryngology Head and Neck Surgery，Kunming Children's Hospital，（Children's Hospital Affiliated to Kunming Medical University），Kunming，650228，China.
Department of Otolaryngology Head and Neck Surgery，Zhaotong First People's Hospital.
Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2021 Jul;35(7):621-626. doi: 10.13201/j.issn.2096-7993.2021.07.010.
To identify gene mutation and analysis the association between clinical characterizes and the mutations in a family of Waardenburg syndrome （WS） type I in Yunnan, China. With informed consent, the proband with WS phenotype and his family members were given medical history collection, physical examination and audiological evaluation. Peripheral blood was obtained, genomic DNA was extracted, and deafness related genes were detected by high-throughput sequencing. Sanger sequencing was used to verify the mutation sites of proband and his family members. C. 602C>G mutation in exon 5 of gene was identified, which is nonsense mutation and may cause a truncated protein. The mutation cause 201 amino acid of the protein changed from serine to stop codon. According to the American College of Medical Genetics and Genomics （ACMG）, it is considered as Pathogenicity（PVS1+PM2+PP3）. This mutation has not been included in the database also not been reported in the literature. Combined with the results of clinical diagnosis and gene diagnosis, this mutation was considered as the cause of the disease. This study enriched mutation spectrum of gene.
为鉴定中国云南一个Ⅰ型瓦登伯革氏综合征（WS）家系中的基因突变，并分析临床特征与突变之间的关联。在获得知情同意后，对具有WS表型的先证者及其家庭成员进行病史采集、体格检查和听力学评估。采集外周血，提取基因组DNA，通过高通量测序检测耳聋相关基因。采用桑格测序法验证先证者及其家庭成员的突变位点。在基因的第5外显子中鉴定出C. 602C>G突变，这是一种无义突变，可能导致截短蛋白。该突变导致蛋白质的第201个氨基酸从丝氨酸变为终止密码子。根据美国医学遗传学与基因组学学会（ACMG）的标准，该突变被判定为致病突变（PVS1+PM2+PP3）。此突变未被纳入数据库，也未在文献中报道。结合临床诊断和基因诊断结果，该突变被认为是致病原因。本研究丰富了该基因的突变谱。
