Distribution characteristics and correlation analysis of GJB2 variation in patients with auditory neuropathy
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摘要: 目的 探究 GJB2基因与听神经病之间的关系, 为此类患者及家庭的遗传咨询提供参考。方法 对117例听神经病患者的基本信息、听力学资料(包括纯音测听、畸变耳声发射、听性脑干反应、耳蜗电图)、影像学资料、遗传学检测等数据进行收集, 并筛选出携带 GJB2基因变异的患者对其进行听神经病相关分析。结果 共计16例患者检出 GJB2基因变异, 变异位点致病性均为致病的或可能致病的, 其中1例为 GJB2[c.427C>T][c.358_360del]复合杂合变异, 听力学表现为全聋, 1例为 GJB2[c.299_300delAT][c.35_36insG]复合杂合变异, 听力学表现为重度听力损失, 其余14例携带 GJB2基因变异患者听力学表型均为典型听神经病。结论 本研究初步分析了 GJB2基因与听神经病的相关性, 并阐述了 GJB2基因变异可能与听神经病表型相关的致病机制。Abstract: Objective To elucidate the correlation between the GJB2 gene and auditory neuropathy, aiming to provide valuable insights for genetic counseling of affected individuals and their families.Methods The general information, audiological data(including pure tone audiometry, distorted otoacoustic emission, auditory brainstem response, electrocochlography), imaging data and genetic test data of 117 auditory neuropathy patients, and the patients with GJB2 gene mutation were screened out for the correlation analysis of auditory neuropathy.Results Total of 16 patients were found to have GJB2 gene mutations, all of which were pathogenic or likely pathogenic.was Among them, one patient had compound heterozygous variants GJB2[c.427C>T][c.358_360del], exhibiting total deafness. One was GJB2[c.299_300delAT][c.35_36insG]compound heterozygous variants, the audiological findings were severe hearing loss.The remaining 14 patients with GJB2 gene variants exhibited typical auditory neuropathy.Conclusion In this study, the relationship between GJB2 gene and auditory neuropathy was preliminarily analyzed, and explained the possible pathogenic mechanism of GJB2 gene variants that may be related to auditory neuropathy.
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Key words:
- auditory neuropathy /
- GJB2 /
- genetic factors
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表 1 GJB2 基因变异携带或复合杂合患者基因信息
编号 国家 性别 发病年龄/岁 检测年龄/岁 GJB2变异 核苷酸 氨基酸 致病性 1006855 中国 男 2.5 2.5 c.88A>G p.Ile30Val VUS 1007131 中国 男 2.5 14.0 c.427C>T p.Arg143Trp P c.358_360del p.Glu120del P 1507400 中国 男 25.0 26.0 c.416G>A p.Ser139Asn LP 1607577 中国 男 25.0 25.0 c.416G>A p.Ser139Asn P 1707823 中国 男 0 65.0 c.416G>A p.Ser139Asn P 1808071 中国 女 13.0 15.0 c.235delC p.Leu79CysfsTer3 P 1908250 中国 男 0 0.5 c.235delC p.Leu79CysfsTer3 P 1908462 中国 女 0 2.0 c.299_300delAT p.His100ArgfsTer14 P 2008588 中国 男 0 3.0 c.235delC p.Leu79Cysfs*3 P 2108673 中国 男 5.0 5.0 c.109G>A p.Val37Ile P 2108924 中国 男 6.0 10.0 c.299_300delAT p.His100Argfs*14 P c.35_36insG p.Val13Cysfs*35 P 2209055 中国 男 0 1.0 c.109G>A p.Val37Ile P 2209171 中国 男 0 6.0 c.-23+1G>A / P 2209213 中国 男 29.0 36.0 c.109G>A p.Val37Ile P 2309264 中国 女 3.0 4.0 c.109G>A p.Val37Ile P 2309270 中国 女 0 3.0 c.571T>C p.Phe191Leu VUS P为致病性，LP为可能致病，VUS为意义未明。 
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表 2 文献报道过的GJB2纯合及复合杂合患者听神经病致病位点
参考文献 致病位点 OAE
(左)OAE
(右)ABR
(左)ABR
(右)临床表现 ECochG
(CM左)ECochG
(CM右)ECochG
(CAP左)ECochG
(CAP右)本文 c.427C>T/c.358_360del Y Y N N 双耳全聋 Y N N N 本文 c.299_300delAT/c.35_36insG Y Y N N 双耳重度听力损失 / / / / Cheng X等[11] 35delG/V95M Y Y N N 双耳中度听力损失 / / / / Santarelli R等[12] 35delG/35delG Y N N N 右耳重度听力损失左耳中度听力损失 Y Y Y N Santarelli R等[12] 35delG/35delG Y Y N N 双耳重度听力损失 Y Y N Y
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