中国赤峰地区耳聋患者病因分析

Etiologic analysis of severe to profound hearing loss patients from Chifeng city in Inner Mongolia

目的探讨中国北方赤峰地区的重度、极审度感音神经性聋患者的耳聋病因构成，了解遗传性聋的比例，为建立和完善符合中国耳聋人群遗传特征的基因筛查程序提供参考。方法凋查对象来自内蒙古赤峰地区某特教学校耳聋患者共134例，听力检查全部为重度、极重度感音神经性聋；对照组100例，为中闰北方听力正常者。所有受柃者均采集外周血并提取DNA，进行GJB2、GJB3、G．IB6、SLC26A4、线粒体DNA（mitochondrial DNA，mtDNA）12SrRNA和tRNASer（UCN）编码区全长序列分析，并对携骷SLC26A4突变的个体凹访进行高分辨率颞骨CT检查。结合耳聋病史、家族史、氨基糖甙类药物应用史及基因筛查结果分析该耳聋人群的病因。结果该耳聋人群中与遗传因素有关的耳聋比例为60．45％（81／134），其中病因明确的遗传性聋比例为33．58％（45／134）。GJ82突变是该人群中17．16％（23／134）耳聋患者的病因；与药物性耳聋相关的线粒体基因1555A〉G突变仅占0．76％（1／134）；通过SLC26A4序列分析结合内耳影像学检查，诊断前庭水管扩大和（或）内耳畸形患者20例，占该耳聋人群的14．93％。此外，还有13．43％（18／134）的患者携带GJB2单杂合突变，其耳聋可能与之有关；6．72％（9／134）的耳聋患者携带SLC26A4单杂合突变，这部分患者颞骨CT检查木发现前庭水管扩大或因故未能进行颞骨CT检查，不排除其耳聋与SLC26A4相关的可能；2．24％（3／134）的耳聋患者携带线粒体12SrRNA1095T〉C突变，该突变与药物性耳聋有关，很可能是导致耳聋的病因。GJB3基因突变可能参与了1．49％（2／134）患者的耳聋发病；在该耳聋人群中未检出GJB6基因突变。结论赤峰地区抽样涮A耳聋群体中遗传性聋比例高达60．45％，GJB2突变是陔人群遗传性聋的最常见病因，SLC26A4突变为第二常见病因。

Objective To investigate the etiology of patients with severe to profound hearing loss and to identify the ratio of hereditary hearing loss in Chifeng area in Northern China. Methods DNA were extracted from peripheral blood of 134 deaf patients from Chifeng special educational school and 100 normal hearing controls in Northern China. Audiology examinations showed that all patients had severe to profound bilateral sensorineural hearing impairment. Sequence analysis of the whole coding areas of GJB2, GJB3, GJB6, SLC26A4, mtDNA12SrRNA and mtDNAtRNASer（UCN） were performed. Individuals carrying SLC26A4 mutation were given further temporal bone CT scan. Results The ratio of hearing loss related to genetic factors in this population was 60. 45% （81/134）. About 33.58% （45/134） of the patients were given accurate genetic diagnosis. GJB2 mutations were responsible for approximately 17. 16% of the cases in ChiFeng area. By screening SLC26A4 followed by temporal bone CT scan, we diagnosed 20 cases of enlarged vestibular aqueduct （EVA） and/or other inner ear malformation. SLC26A4 mutations account for about 14.93% of the cases. The aminoglycoside-related mtDNA 1555A 〉 G mutation accounted for 0. 76% of the cases in Chifeng area. In addition, another 13.43% （18/134） of the cases carried heterozygous GJB2 mutation and their heating loss may be related to GJB2. 6. 72% （9/134） of the cases carried heterozygous SLC26A4 mutation who were not found EVA by temporal bone CT or not took CT examination for some reasons. However, their heating loss may also he SLC26A4-related. About 2. 24% （ 3/134 ） of the cases carried mtDNA 12SrRNA 1095 T 〉 C which may also be an aminoglycoside-related mutation and very likely he the cause of heating loss. GJB3 might participate in the pathomeehanism of heating loss in 1.49% （2/134） of the patients. GJB6 mutation was not detected in this population. Conclusions The ratio of heating loss related to genetic factors in the sample drawing population from Chifeng was 60. 45% （ 81 cases）. GJB2 is the most common gene and SLC26A4 is the second common gene next to GJB2 that cause deafness in this area.