两个Ⅱ型Waardenburg综合征家系SOX10基因突变分析  

SOX10 Gene Variation in Two Families with Waardenburg Syndrome TypeⅡ

作　　者：毕辉 张贵鹏 马秀丽 毕先云 刘晖 马静[4] BI Hui;ZHANG Guipeng;MA Xiuli;BI Xianyun;LIU Hui;MA Jing(Graduate School of Dali University,Dali 671003;People's Hospital of Chuxiong Yi Autonomous Prefecture,Chuxiong 675099;Xiangyun People’s Hospital,Xiangyun 672199;Department of Otorhinolaryngology Head and Neck Surgery,Kunming Children′s Hospital,Kunming Key Laboratory for Prevention and Control of Congenital Birth Defects in Children,Kunming 650228)

机构地区：[1]大理大学研究生院,大理671003 [2]楚雄彝族自治州人民医院,楚雄675099 [3]祥云县人民医院,祥云672199 [4]昆明市儿童医院耳鼻咽喉头颈外科昆明市儿童先天出生缺陷防控研究重点实验室,昆明650228

出　　处：《中华耳科学杂志》2023年第1期57-63,共7页Chinese Journal of Otology

基　　金：云南省中青年学术和技术带头人后备人才培养项目(2019HB102);云南省高层次卫生健康技术人才培养专项(L-2019002);云南省王海波专家工作站(202105AF150056)。

摘　　要：目的通过对云南地区2例Ⅱ型Waardenburg综合征(Waardenburg syndrome typeⅡ,WS2)患者相关基因突变位点进行分析,探讨WS2可能的分子致病原因。方法经知情同意,对具有Waardenburg综合征(waardenburg syndrome,WS)表型的先证者及其家属进行病史采集、体格检查、听力学评估、影像学检查。获取外周血,提取基因组DNA,高通量测序方法对耳聋相关基因进行检测,对先证者及其家属进行突变位点的Sanger测序验证分析。结果两个家系中有4名患者临床表现出虹膜异色和感音神经性耳聋,诊断为WS2。二代测序检出先证者1SOX10基因c.255G>A变异,为无义突变,导致所编码的蛋白质发生截短,可能丧失正常功能,该变异来自其母亲。先证者2及其父亲检测出SOX10基因c.1393C>T变异,为临床意义未明的变异,生物信息软件预测其致病可能性较高,该位点在多个物种间保守性高。结论基因检测可以辅助诊断Waardenburg综合征,SOX10基因c.255G>A、c.1393C>T杂合突变可能是本研究两个家系中WS2患者的分子致病原因。Objective To report gene mutation sites in two Yunnan families with Waardenburg syndrome typeⅡ(WS2)as potential molecular biological etiologies.Methods With informed consent,medical history collection,physical examination and audiological evaluation and imaging studies were completed in the probands with WS phenotype and their family members.Peripheral blood was obtained and genomic DNA extracted for detection of deafness related genes by high-throughput sequencing.Sanger sequencing was used to verify the mutation sites.Results Four patients were diagnosed with WS2 based on clinical manifestations of heterochromia iridum and sensorineural deafness.Proband1 had SOX10 gene nonsense mutation c.255G>A inherited from her mother,who was also diagnosed with WS2,resulting in truncation of the encoded protein and possibly loss of normal function.Proband 2 and his father had SOX10 gene c.1393C>T variation,a variant of uncertain significance(VUS),although bioinformatics software predicted a higher risk with this variation.This locus is highly conserved in multiple species.Conclusion Gene sequencing can assist diagnosis of WS.In this study,SOX10 gene c.255G>A and c.1393C>T heterozygous variations may be the molecular cause for WS manifestations in the two families.

关 键 词：听力损失 感音神经性 WAARDENBURG综合征 SOX10基因 DNA突变分析 

分 类 号：R764[医药卫生—耳鼻咽喉科]