Objective To analyze the deafness gene mutations in children with non-syndromic hearing impairment (NSHI), and to investigate the genetic etiology and features of deafness disorders at the molecular level. Methods 94 children with NSHI diagnosed by The Center of Diagnosis and Treatment of Children's Hearing Disorders in Tianjin were screened for 20 hotspot of hearing loss-associated mutations from GJB2, GJB3, SLC26A4 and mitochondrial 12S rRNA (MTRNR1) using the matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). The data of genetic screening was analyzed with correlation to audiologic testing results. Results In 94 cases with moderate to profound sensorineural hearing loss, 73 of which presented with bilateral sensorineural hearing loss, and 21 with unilateral hearing loss. Deafness gene mutations were found in 31 subjects (32.98%, 31/94), 13 of which with sin-gle gene homozygous mutations, 9 of which with single gene and double-site heterozygous mutations, and 9 with sin-gle-gene and single-site mutations. The positive detective rate of deafness gene mutations in bilateral hearing loss group was 42.47%but no deafness gene was detected in unilateral hearing loss group. The positive detective rate of GJB2 and SLC26A4 in 94 subjects were 17.02%and 15.96%respectively, and no mutations found on GJB3 and MTRNR1. Sixteen subjects showed GJB2 mutations, 8 of which with homozygous mutations, 5 with double-site heterozygous mutations, and 3 with single-site heterozygous mutations. Fifteen subjects with bilateral hearing loss were SLC26A4 (PDS)-positive,5 of which were homozygous (at IVS7-2A>G), 4 subjects with double-site heterozygous mutations, and 6 subjects with single-site heterozygous mutations. The positive detective rates for GJB2 and SLC26A4 genes in the bilateral hearing loss group are 21.92% and 20.55% respectively, however these genes were not detected in the unilateral hearing loss group. Conclusions High proportion of etiologies in patients with NSHI were due to genetic factors. The heritability of bilateral deafness was higher than that of unilateral hearing loss. Regularly audiology follow-up for bilateral deafness and deafness gene-positive children was of great significance. The union screening could provide theoretical and practi-cal basis for the three level preventive measures to reduce birth defects.%目的分析非综合征性听力障碍儿童耳聋基因突变情况,从分子水平探究该人群聋病的遗传病因和特点,为早期诊断、治疗及预防先天性和遗传性耳聋提供科学依据.方法采用基质辅助激光解吸电离飞行时间质谱(MALDI-TOF MS)技术,对天津市儿童听力障碍诊治中心诊断的94例非综合征性听力障碍儿童进行常见耳聋基因(GJB2、GJB3、SLC26A4、线粒体12SrRNA)共20个突变位点的检测,并对检测结果及听力学资料进行统计学分析.结果94例研究对象皆为中度、重度及极重度感音神经性耳聋,其中双侧听力下降组73例,单侧听力下降组21例.94例患儿中31例(32.98%,31/94)检出携带耳聋易感基因突变,单基因纯合突变13例,单基因复合杂合突变9例,单杂合突变9例,其中双侧听力下降组耳聋基因阳性率(42.47%)明显高于单侧听力下降组(0.00%)(χ2=13.31,P<0.01).GJB2基因、SLC26A4基因、GJB3基因及12SrRNA的突变检出率分为17.02%、15.96%、0.00%和0.00%.GJB2阳性例数16例,皆位于双侧听力下降组,其中纯合突变8例,复合杂合突变5例,杂合突变3例.SLC26A4(PDS)基因阳性例数15例,皆位于双侧听力下降组,其中纯合突变者5例(皆位于IVS7-2A>G位点),复合杂合突变者4例,杂合突变者6例.双耳听力下降组的GJB2基因阳性检出率(21.92%)高于单耳听力下降组(0.00%)(P<0.05);SLC26A4基因阳性检出率两组间比较无明显差别(20.55%,0.00%)(P>0.05).结论遗传因素在非综合征性耳聋的致聋病因中所占比例较高,双侧聋遗传性高于单侧聋,对于双侧耳聋及耳聋基因阳性患儿定期进行听力学随访意义重大,耳聋基因筛查是对常规听力学筛查的有效补充,可为降低出生缺陷的三级预防措施提供理论和实践依据.
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