摘要目的 探讨携带GJB2基因突变的非综合征型耳聋先证者及其家系成员的基因型与临床上听力损失程度的相关性.方法 2006年4月至2012年9月期间共筛查出221例携带GJB2基因突变的非综合征型耳聋先证者及家系成员,根据GJB2突变对其蛋白产物的影响以及是否携带235delC进行分组.其中按非截断突变(non-truncating,NT)和截断突变(truncating,T))分为T/T组、T/NT组和NT/NT组,按是否携带235delC分为235delC/235delC组、235deIC/Non-235del组和Non235 delC/Non-235 delC组,分别对其听力学检测结果进行整理和分析.结果 按是否截断突变分组:Fisher精确概率法统计分析表明,三组间听力损失程度不符合随机分布(P =0.003),其中T/T组的听力损失程度明显高于T/NT组和NT/NT组(P值均＜0.01).按是否携带235delC突变分组:三组间听力损失程度的差异有统计学意义,分别进行两两比较(Fisher精确概率法)发现235delC/235delC组的听力损失程度明显高于235delC/Non-235delC组和Non-235 delC/Non-235 delC组(P值均＜0.01),235delC/Non-235delC组的听力损失程度高于Non-235 delC/Non-235 delC组(P =0.033).在GJB2纯合突变和复合杂合突变基因型中,G109A/G109A、235delC/512insAACG、299delAT/G109A和235delC/G109A等基因型导致的听力损失程度明显低于235delC/235delC组.结论 与235delC复合杂合突变及非235delC突变的患者相比,235delC纯合突变的患者表现出更为严重的听力损失.GJB2基因截断突变患者的听力损失程度较非截断突变患者更重.

abstractsObjective To assess the possible genotype-phenotype correlation for GJB2.Methods Retrospectively analyzed GJB2 gene mutations with non-syndromic hearing impairment (NSHI) patients and their families audiological data.Individuals were grouped,according to non-truncated mutant (nontruncating,NT) and truncating mutations (truncating,T),into T/T group,T/NT group and NT/NT group.And according to whether they carry 235delC,grouped into 235delC/235delC group,235de1C/Non-235de1 group and Non-235delC/Non-235delC group.Results Grouped according to whether the truncation mutants:Fisher exact statistical analysis showed that the degree of hearing loss among the three groups did not meet the random distribution (P =0.003),T/T group was significantly higher than T/NT group (P =0.000) and NT/NT group (P =0.000) on the degree of hearing loss.Grouped according to whether they carry 235delC mutation:degrees of hearing loss among the three groups were statistically significant differences.Respectively pairwise comparisons (Fisher exact test) found 235delC/235delC group was significantly higher than 235delC/Non-235delC on the degree of hearing loss group (P =0.001) and Non235delC/Non-235delC group (P =0.000),235delC/Non-235delC group higher than Non-235delC/Non235delC group (P =0.033).In GJB2 mutations homozygous and compound heterozygous mutation genotype:G109A/G109A,235delC/512insAACG,299delAT/G109A and 235delC/G109A degree of hearing loss caused by genotype was significantly lower than 235delC/235delC group.Conclusions 235delC homozygotes have significantly more hearing impairment,when compared with 235delC/non235delC compound heterozygotes.People with two non-235delC mutations have even less hearing impairment.Patients with non-truncation mutants (G109A) suffer from lighter hearing loss than truncation mutations(235delC,299delAT).