不同年龄段非综合征性耳聋常见基因检测及临床表型分析  

Prevalence of common genetic mutations and clinical characteristics analysis in patients at different ages with nonsyndromic hearing impairment

作　　者：张初琴[1] 陈波蓓[1] 陈迎迎[1] 刘学军[1] 郑静[2] 高金建[1] 黄赛瑜[1] 南奔宇[1] 章誉耀[1] 余啸[1] 管敏鑫[2,3] 

机构地区：[1]温州医学院附属二院&附属育英儿童医院耳鼻喉科,温州325027 [2]温州医学院浙江省医学遗传学重点实验室,温州325027 [3]浙江大学生命科学学院,杭州310000

出　　处：《遗传》2013年第3期352-358,共7页Hereditas（Beijing)

基　　金：浙江省自然基金课题(编号:LY12H130001);浙江省计生委课题(编号:200914)资助

摘　　要：为了探讨非综合征性耳聋易感基因检出率与年龄因素的相关性及其发病特点,文章收集了2006年4月～2012年4月在温州医学院附属第二医院就诊的215名非综合征性耳聋患者,按就诊年龄和发病年龄分别分为成人组（〉18岁）及未成人组,后者又分为婴幼儿组（0~3岁）、学龄前组（3~6岁）、学龄组（6~18岁）,提取基因组DNA,然后进行GJB2和线粒体DNA A1555G/C1494T基因检测,并对其阳性检出率及年龄构成比进行统计学分析。结果显示,GJB2基因突变的检出率为18.14%,线粒体DNAA1555G/C1494T基因突变为11.16%;就诊年龄为成人组的GJB2基因突变检出率低于未成人组（分别是5.26%,22.36%）,线粒体DNA A1555G/C1494T基因突变则高于未成人组（分别是31.48%,4.97%）,组间有统计学差异（χ2分别为7.108、20.852,P分别为0.008、0.000）;发病年龄为成人组及未成人组GJB2基因突变的阳性检出率分别为0%和20.10%,组间有统计学差异（χ2=5.157,P=0.023）,而线粒体DNA A1555G/C1494T突变的阳性检出率分别为14.29%和11.34%,组间无统计学差异（χ2=0.160,P=0.698）;GJB2基因突变的患者发病年龄多集中在l岁以内（66.67%）;线粒体DNA A1555G/C1494T突变在各个年龄段均可发病,l岁以内仅占28.00%,3岁以后占40.00%,两者在年龄构成比上有统计学差异（χ2=11.035,P=0.004）;采用不同耳聋分级标准判断携带线粒体DNA A1555G/C1494T基因突变者的听力损失程度,结果有统计学差异。这表明GJB2基因突变主要表现为先天性耳聋;线粒体DNA A1555G/C1494T基因突变不仅可表现为先天性耳聋,也可表现为后天进行性耳聋,氨基糖苷类抗生素在其各个年龄段均可诱发或加重耳聋,对其进行听力检测要重视4～8 kHz频率段;新生儿听力筛查联合基因筛查对早期发现遗传性耳聋具有重要的意义。To evaluate the correlation between genetic mutations and the age in nonsyndromic hearing impairment （NSHI） and the clinical characteristics of NSHI, 215 patients with NSHI were enrolled between April 2006 and April 2012. All patients were divided into four groups according to ages of hearing loss onset and clinic presentation （0-3, 3-6, 6-18 and 18＋ years）. The mutations of GJB2 and mitochondria DNA （mtDNA） 1555G/C1494T were screened from peripheral blood samples in each age group. The prevalence of mutations and the age ratio were obtained. The study showed that 18.14% of all patients were found to have GJB2 mutations and 11.16% were found to have mtDNA A1555G/C1494T mutations. The prevalence of GJB2 mutation in adult group （5.26%） was lower than juvenile group who sought medical attention at 0-18 years of age （22.36%）, while the prevalence of mtDNA A1555G/C 1494T in adult group （31.48%） was higher than juvenile group （4.97%）. Significant differences in the prevalence of GJB2 （X^2=7.108, P=0.008） and mtDNA A1555G/C1494T （Z2=20.852, P=0.000） were observed in both of two groups. The prevalence of GJB2 mutations between adult and juvenile groups according to ages of hearing loss onset was statistically significant different （0%, 20.10%, respectively, and P=0.023）, while the prevalence of mtDNA A1555G/C1494T mutations was not different （14.29%, 11.34%, respectively, and P=0.698）. The onset age of 66.67% of patients with GJB2 mutations was less than 1 year old, while the onset of pa- tients with mtDNA A 1555G/C 1494T mutations could be found at any age group. Different standardizations of hearing loss could also show different results. These data strongly suggest that most of GJB2 mutations are found in congenital deafness and mtDNA A1555G/C1494T mutations mainly represent acquired deafness, which can be induced or aggravated by ami- noglycoside antibiotics in all age groups and should be tested mainly ranging from 4 kHz to 8 kHz. Both newborn hearing screening and genet

关 键 词：非综合征性耳聋 GJB2 线粒体DNA 突变 基因诊断 

分 类 号：R764.43[医药卫生—耳鼻咽喉科]