感音神经性聋患者内耳CT表型与SLC26A4基因型关系探讨

目的 分析感音神经性聋患者内耳高分辨率螺旋CT(下简称CT)表型与SLC26A4基因致病性突变类型之间的关系,探讨前庭导水管扩大相关内耳畸形患者SLC26 A4基因检测辅助CT诊断的可行性.方法 以Sennaroglu2010分类为标准分析2 705例感音神经性聋患者内耳CT表型,并采用DNA测序的方法检测全部患者SLC26A4基因致病性突变检出率及突变类型,统计该基因突变在患者各类内耳CT表型中的分布特点,分析SLC26A4基因突变类型与CT表型之间的关系.结果 ①2 705例患者中CT诊断为内耳畸形826例(30.54％,826/2 705),其中耳蜗畸形446例:Michel畸形5例、耳蜗未发育12例、共同腔畸形6例、耳蜗发育不全畸形34例(CH-Ⅰ 9例、CH-Ⅱ 8例、CH-Ⅲ 17例)、耳蜗分隔不全畸形389例(IP-Ⅰ 22例、IP-Ⅱ 352例、IP-Ⅲ 15例);非耳蜗畸形380例(前庭导水管扩大340例,单纯前庭、半规管、内听道畸形40例);内耳CT正常1 879例.②共检出SLC26A4基因双等位基因致病性突变517例,其中纯合突变164例、复合杂合突变353例,均在前庭导水管扩大相关内耳畸形患者(IP-Ⅱ 264例,前庭导水管扩大253例)中检出,在本组前庭导水管扩大相关内耳畸形患者中检出率为74.71％ (517/692).结论 SLC26A4基因致病性突变与前庭导水管扩大相关内耳畸形密切相关,SLC26A4基因检测在前庭导水管扩大相关内耳畸形患者中可辅助CT成为诊断工具.

The Relationship between the CT Phenotypes of the Inner Ear and Pathogenic Mutations of SLC26A4 in Patients with Sensorineural Hearing Loss

Objective To explore the relationship between the CT phenotypes of the inner ear and pathogenic mutations of SLC26A4,and analyze the feasibility of using the method of gene sequence analysis to help CT examination in diagnosing part of patients related to vestibular aqueduct malformation with sensorineural hearing loss.Methods A retrospective review of CT findings relating to 2 705 cases of outpatients was carried out.The inner ear malformations diagnosed by CT were classified according to the methods proposed by Sennaroglu 2010.The DNA sequence of SLC26A4 was analyzed in those patients to explore the relationship between the CT phenotypes and the pathogenic mutations of SLC26A4.Results A total of 826 cases of the inner ear malformations were found in 2 705 cases of patients with sensorineural hearing loss by CT examination.The 446 cases of cochlear malformation consisted of the follow types:5 cases of Michel deformity,12 cases of cochlear aplasia,6 cases of common cavity deformity,34 cases of cochlear hypoplasia (CH-Ⅰ type was 9 cases,CH-Ⅱ type was 8 cases and CH-Ⅲ type was 17 cases),389 cases of cochlear incomplete partition (22 cases of IP-Ⅰ type,352 cases of IP-Ⅱ type,15 cases of IP-Ⅲ type).The 380 cases of non-cochlea malformation consisted of the follow types:340 cases of large vestibular aqueduct,40 cases of simple vestibular/semicircular canal/internal auditory canal malformation,and 1 879 normal cases.The DNA sequence results revealed that 517 cases carried pathogenic mutations (B i-allelic mutations) of SLC26A4,among which 164 cases were homozygous and 353 cases were compound heterozygous.Pathogenic mutations of SLC26A4 detected 100 ％ (517/517) in the group related to vestibular aqueduct malformation and the positive rate was 74.71 ％ (517/692).Conclusion The results suggested that pathogenic mutations of SLC26A4 were closely related to the CT phenotypes of vestibular aqueduct malformation.An analysis of SLC26A4 can help CT examination to diagnose part of patients related to vestibular aqueduct malformation with sensorineural hearing loss.