两个鳃耳综合征家系的临床表型及致病变异分析  

Analysis of Clinical Phenotype and Pathogenic Variations in Two Families with Branchio-oto Syndrome

作　　者：何万里 许红恩 刘梦丽 张腾 孙淑萍[1] 卢伟[1] He Wanli;Xu Hong'en;Liu Mengli;Zhang Teng;Sun Shuping;Lu Wei(Department of Otorhinolaryngology,the First Affiliated Hospital of Zhengzhou University,Zhengzhou,450052,China;不详)

机构地区：[1]郑州大学第一附属医院耳鼻喉医院耳科,郑州450052 [2]郑州大学医学科学院精准医学中心

出　　处：《听力学及言语疾病杂志》2024年第3期206-211,共6页Journal of Audiology and Speech Pathology

基　　金：河南省高等院校重点科研项目(22A320026);河南省医学科技攻关计划省部共建重点项目(SBGJ202302061)。

摘　　要：目的探寻两个鳃耳综合征家系的致病原因。方法收集2个家系临床资料,利用全外显子组测序和Sanger测序技术检测和验证鳃耳综合征致病基因和变异。结果2个家系中,先证者1为先天性重度感音神经性听力下降,伴耳前瘘管及颈前瘘管;先证者2在5岁时发现双耳听力下降并渐进性加重,伴耳前瘘管及颈前囊肿,现双耳为重度混合性听力损失;两例先证者均被诊断为鳃耳综合征。基因检测结果示,先证者1携带EYA1基因的无义变异:NM_000503.6:c.1408G>T(p.Glu470Ter),先证者2携带EYA1基因的无义变异:NM_000503.6:c.889C>T(p.Arg297Ter),根据美国医学遗传学和基因组学学会(ACMG)指南上述变异均评级为致病变异。c.1408G>T基因变异既往未见报道,c.889C>T基因变异为已知变异。结论EYA1基因的c.1408G>T(p.Glu470Ter)变异和c.889C>T(p.Arg297Ter)变异是本研究两个家系鳃耳综合征的致病原因。Objective To study the causes of two Chinese families with Branchio-oto syndrome.Methods The clinical data of two families were collected,and the pathogenic genes and variants of Branchio-oto syndrome were screened and verified by whole exome sequencing and Sanger sequencing.Results Two proband patients were diagnosed with Branchio-oto syndrome.Proband 1 presented with preauricular and anterior cervical fistulas,as well as congenital severe sensorineural hearing loss.On the other hand,proband 2 displayed a preauricular fistula and an anterior cervical cyst.At the age of 5,progressive deterioration of binaural hearing was observed,leadingtothe current diagnosis of severe mixed deafness.Genetic analysis showed that proband 1 and 2 carried nonsense variants of EYA1 gene:NM_000503.6:c.1408G>T(p.Glu470Ter),and c.889C>T(p.Arg297Ter).According to the guidelines of the American College of Medical Genetics and Genomics(ACMG),the above variants were rated as pathogenic variants.After reviewing the literature,the c.1408G>T variant had not been previously reported,and the c.889C>T is a known variant.Conclusion The variants c.1408G>T(p.Glu470Ter)and c.889C>T(p.Arg297Ter)of EYA1 gene are the cause of these two families with Branchio-oto syndrome.The first report of c.1408G>T broadens the mutational spectrum of EYA1 gene and provids a clinical reference for the diagnosis of Branchio-oto syndrome.

关 键 词：鳃耳(肾)综合征 EYA1基因 基因变异 

分 类 号：R764.431[医药卫生—耳鼻咽喉科]