Clinical hearing phenotypes analysis of GJB2 gene p.V37I homozygote and compound heterozygote mutation in infants
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摘要: 目的 分析GJB2基因p.V37I纯合及复合杂合突变者的听力表型，旨在为遗传咨询提供参考。方法 研究对象为2023年1月-2024年3月在北京同仁医院耳鼻咽喉头颈外科确诊为GJB2基因p.V37I纯合及复合杂合突变患儿53例，患儿均接受了新生儿听力筛查、23项耳聋基因筛查及听力学检查(听性脑干反应、声导抗、畸变产物耳声发射、听性稳态反应)。对比分析纯合突变组(30例)与复合杂合突变组(23例)的新生儿听力筛查及各项听力学诊断结果。结果 53例中，总体新生儿听力筛查未通过率为64.15%(34/53)，纯合突变组未通过率80.00%(24/30)高于复合杂合突变组43.48%(10/23)，2组差异有统计学意义(P < 0.05)。3例p.V37I复合杂合突变者新生儿听力筛查通过，诊断为单侧轻度听力损失。53例平均确诊月龄为(3.77±1.40)个月，确诊听力损失25例(47.17%，25/53)，其中单侧13例，双侧12例；听力正常28例(52.83%，28/53)。确诊听力损失比例，纯合突变组(56.67%，17/30)与复合杂合突变组(34.78%，8/23)差异无统计学意义(P>0.05)。听力损失25例(37耳)中，轻度、中度及极重度听力损失占比分别为70.27%(26/37)、27.03%(10/37)、2.70%(1/37)。纯合突变组与复合杂合突变组听力损失程度均以轻度为主，占比分别为70.37%(19/27)及70.00%(7/10)，2组差异无统计学意义(P>0.05)。结论 GJB2基因p.V37I纯合及复合杂合突变者婴儿期以轻度听力损失为主，纯合及复合杂合突变者出现听力损失的概率及听力损失程度无明显差异。对目前听力诊断正常的p.V37I纯合及复合杂合突变者，需要临床持续随访。Abstract: Objective To analyze the hearing phenotypes of p. V37I homozygote and compound heterozygote mutation in GJB2 gene, and to provide basis for genetic counseling.Methods Fifty-three subjects with p. V37I homozygote and compound heterozygote mutation were recruited at Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital from January 2023 to March 2024. All subjects received universal newborn hearing screening(UNHS), 23-site chip neonatal deafness genetic screening and audiological tests, including ABR, acoustic immittance, DPOAE, ASSR. The results of newborn hearing screening and hearing diagnosis were compared between homozygous mutation group of 30 cases and compound heterozygous mutation group of 23 cases.Results In 53 cases, the overall refer rate of UNHS was 64.15%(34/53), the refer rate of homozygous mutation group was 80.00%(24/30), which was higher than that of compound heterozygous mutation group(43.48%, 10/23), the difference between the two groups was statistically significant(P < 0.05). Three subjects with p. V37I compound heterozygous mutation had passed UNHS and diagnosed with unilateral mild hearing loss. The average age of diagnosis of 53 cases was (3.77±1.40) months, 25 cases with hearing loss accounted for 47.17%, including 13 cases with unilateral, 12 cases with bilateral, 28 cases with normal hearing accounted for 52.83%. There was no significant difference between homozygous mutation group(56.67%, 17/30) and compound heterozygous mutation group(34.78%, 8/23) in the proportion of confirmed hearing loss(P>0.05). Among 37 ears of 25 patients with hearing loss, the proportion of mild, moderate and profound hearing loss were 70.27%(26/37), 27.03%(10/37) and 2.70%(1/37), respectively. The hearing loss degree of the homozygous mutation group and the compound heterozygous mutation group were mainly mild, accounting for 70.37%(19/27) and 70.00%(7/10) respectively. There was no significant difference between the two groups in the distribution of hearing loss degree(P>0.05).Conclusion The probability of hearing loss was 47.17% in infants of GJB2 gene p. V37I homozygote and compound heterozygote mutation, mainly mild hearing loss. There was no difference in the probability of hearing loss and the distribution of hearing loss degree between the two groups. Patients with p. V37I homozygous and compound heterozygous mutation currently diagnosed as normal hearing need continuous clinical follow-up.
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Key words:
- GJB2 gene /
- p. V37I /
- hearing phenotypes /
- hearing loss
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表 1 2组基因型分布
组别 基因型 例数 纯合突变组 c.109G>A/c.109G>A 30 复合杂合突变组 c.235delC/c.109G>A 16 c.299_300delAT/c.109G>A_ 5 c.35insG/c.109G>A 1 c.257C>G/c.109G>A 1 合计 53 
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表 2 2组新生儿听力筛查结果比较
例(%) 组别 例数 听力筛查通过 听力筛查未通过 双耳未通过 单耳未通过 纯合突变组 30 6(20.00) 21(70.00) 3(10.00) 复合杂合突变组 23 13(56.52) 9(39.13) 1(4.35) 合计 53 19(35.85) 30(56.60) 4(7.55)
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表 3 2组新生儿听力筛查与听力诊断结果比较
例(%) 组别 新生儿听力筛查 听力诊断 合计 正常 听力损失 纯合突变组 通过 6(100.00) 0(0) 6(100.00) 未通过 7(29.17) 17(70.83) 24(100.00) 复合杂合突 通过 10(76.92) 3(23.08) 13(100.00) 变组 未通过 5(50.00) 5(50.00) 10(100.00)
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表 4 2组听力确诊情况比较
例(%) 组别 例数 正常 听力损失 单侧 双侧 合计 纯合突变组 30 13(43.33) 7(23.34) 10(33.33) 17(56.67) 复合杂合突变组 23 15(65.22) 6(26.09) 2(8.69) 8(34.78) 合计 53 28(52.83) 13(24.53) 12(22.64) 25(47.17)
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表 5 2组听力损失程度比较
组别 听力损失耳数 听力损失程度/耳(%) 轻度 中度 重度 极重度 纯合突变组 27 19(70.37) 7(25.93) 0(0) 1(3.70) 复合杂合突变组 10 7(70.00) 3(30.00) 0(0) 0(0) 合计 37 26(70.27) 10(27.03) 0(0) 1(2.70)
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