Analysis on trend of hearing changes in infants with p.V37I mutation in GJB2 gene at different months of age
-
摘要: 目的 探讨不同月龄GJB2基因p.V37I突变婴幼儿听力变化趋势。方法 研究对象为确诊GJB2基因p.V37I纯合或复合杂合突变患儿54例(108耳)，所有受试者均接受了听性脑干反应、听性稳态反应、声导抗等听力学检测。根据患儿不同月龄分为3组：A组为≤3个月共26例、B组为>3~≤6个月共17例、C组为>6个月共11例。对3组ABR反应阈值、听力程度、ASSR四个频率平均反应阈值、ASSR 500、1 000、2 000、4 000 Hz各频率反应阈值进行统计学分析。结果 54例患儿中，男35例，女19例；年龄2~27个月，中位年龄4个月。3组ABR反应阈值由低到高依次为A组 < B组 < C组，差异有统计学意义(P < 0.05)，组间两两比较C组高于A组(P=0.006)。3组确诊为听力损失占比依次为34.61%、50.00%、63.64%，3组听力程度的差异有统计学意义(P < 0.05)，组间两两比较显示，A组与C组的差异有统计学意义(P=0.012)，A组以听力正常占比最高(65.39%)，C组以轻度听力损失占比最高(45.46%)。3组ASSR四个频率平均反应阈值由低到高依次为A组 < B组 < C组，差异有统计学意义(P < 0.05)，组间两两比较C组高于A组(P=0.002)。3组ASSR各频率反应阈值由低到高均为A组 < B组 < C组，差异均有统计学意义(P < 0.05)，组间两两比较，500 Hz时C组高于A组(P=0.003)与B组(P=0.015)，1 000 Hz(P=0.010)与2 000 Hz(P < 0.001)时C组均高于A组，4 000 Hz时组间比较差异无统计学意义。结论 GJB2基因p.V37I突变婴幼儿随着年龄增长听力损失发生率增加，且听力损失程度加重，听力进展以500、1 000、2 000 Hz为主，提示应定期随访，警惕听力变化。Abstract: Objective To explore the trend of hearing changes in infants with GJB2 gene p.V37I mutation at different months.Methods The subjects were 54 children(108 ears) with p.V37I homozygous or compound heterozygous mutation in GJB2 gene. All the subjects underwent auditory brainstem response, auditory steady-state response, acoustic immittance and other audiological tests. Children were divided into three groups according to their age, 26 cases in group A were ≤3 months old, 17 cases in group B were>3~≤6 months old, and 11 cases in group C were>6 months old. Statistical analysis was performed on the three groups of ABR response threshold, hearing degree, the ASSR average response threshold of four frequencies and the ASSR response thresholds for each frequency of 500, 1 000, 2 000 and 4 000 Hz.Results Among the 54 cases, 35 were male and 19 were female, with an age rang of 2-27 months and a median age of 4 months. The ABR response threshold of the three groups were ranked from low to high as group A, group B and group C, and the difference was statistically significant(P < 0.05). The ABR response thresholds of the three groups were ranked from low to high as group A, group B, and group C. The comparison between groups showed that the ABR response thresholds of group C was higher than that of group A(P=0.006). The proportion of confirmed hearing loss in the three groups was 34.61%, 50.00% and 63.64%, respectively, and the difference of hearing level among the three groups was statistically significant(P < 0.05). The comparison between groups showed that the difference between group A and group C was statistically significant(P=0.012), normal hearing accounted for the highest proportion in group A(65.39%), while mild hearing loss accounted for the highest proportion in group C(45.46%). The ASSR average response thresholds of the four frequencies in the three groups were ranked from low to high as group A, group B and group C, and the difference is statistically significant(P < 0.05). The comparison between groups showed that response ASSR thresholds of group C was higher than that of group A(P=0.002). Response thresholds of ASSR in each frequency in the three groups were all ranked from low to high as in group A, group B and group C, and the differences were statistically significant(P < 0.05). Compared with each other between groups, response ASSR thresholds of group C was higher than those of group A(P=0.003) and group B(P=0.015) at 500 Hz, while response ASSR thresholds of group C was higher than group A at 1 000 Hz(P=0.010) and 2 000 Hz(P < 0.001), and there was no statistical difference at 4 000 Hz.Conclusion The incidence of hearing loss in GJB2 gene p.V37I mutation increased with age, and the degree of hearing loss increased, the hearing progression was mainly 500, 1 000 and 2 000 Hz suggesting regular follow-up and alert to hearing changes.
-
Key words:
- GJB2 gene /
- p.V37I /
- mutation /
- hearing loss
-
-
表 1 ABR反应阈值的比较
dB nHL 组别 耳数 X±S P A组 52 33.85±9.93 B组 34 38.53±14.38 0.022 C组 22 42.27±13.07 合计 108 37.04±12.47 
下载: 导出CSV
表 2 3组听力程度的比较
耳(%) 组别 耳数 正常 轻度 中度 重度 P A组 52 34(65.39) 17(32.69) 1(1.92) 0 B组 34 17(50.00) 12(35.30) 4(11.76) 1(2.94) 0.044 C组 22 8(36.36) 10(45.46) 4(18.18) 0 合计 108 59(54.63) 39(36.11) 9(8.33) 1(0.93)
下载: 导出CSV
表 3 ASSR四个频率平均反应阈值的比较
dB nHL 组别 耳数 X±S P A组 52 27.98±10.37 B组 34 32.72±15.30 0.007 C组 22 39.55±15.40 合计 108 31.83±13.78
下载: 导出CSV
表 4 ASSR各频率反应阈值的比较
dB nHL，X±S 组别 耳数 500 Hz 1 000 Hz 2 000 Hz 4 000 Hz A组 52 29.42±12.27 27.88±13.04 25.38±10.93 29.23±10.64 B组 34 31.76±14.87 29.71±16.23 31.76±17.66 37.65±16.34 C组 22 42.73±17.98 40.00±19.52 37.73±14.45 37.73±16.60 合计 108 32.87±15.15 30.93±16.09 29.91±14.76 33.61±14.43 P 0.010 0.030 0.002 0.027
下载: 导出CSV
-
[1] World Health Organization. World report on hearing[M]. Geneva: World Health Organization, 2021: 14.
[2] Wingard JC, Zhao HB. Cellular and deafness mechanisms underlying connexin mutation-induced hearing loss-A common hereditary deafness[J]. Front Cell Neurosci, 2015, 9: 202.
[3] Adadey SM, Wonkam-Tingang E, Twumasi Aboagye E, et al. Connexin genes variants associated with non-syndromic hearing impairment: a systematic review of the global burden[J]. Life, 2020, 10(11): 258. doi: 10.3390/life10110258
[4] Chen Y, Wang ZL, Jiang Y, et al. Biallelic p. V37I variant in GJB2 is associated with increasing incidence of hearing loss with age[J]. Genet Med, 2022, 24(4): 915-923. doi: 10.1016/j.gim.2021.12.007
[5] 黄丽辉, 韩德民, 刘莎, 等. 未通过听力筛查的婴幼儿听力追踪分析[J]. 中华耳鼻咽喉头颈外科杂志, 2005, 40(9): 643-647.
[6] Norton SJ, Gorga MP, Widen JE, et al. Identification of neonatal hearing impairment: summary and recommendations[J]. Ear Hear, 2000, 21(5): 529-535. doi: 10.1097/00003446-200010000-00014
[7] Shen J, Oza AM, del Castillo I, et al. Consensus interpretation of the p. Met34Thr and p. Val37Ile variants in GJB2 by the ClinGen Hearing Loss Expert Panel[J]. Genet Med, 2019, 21: 2442-2452. doi: 10.1038/s41436-019-0535-9
[8] 文铖, 黄丽辉, 王雪瑶, 等. GJB2基因p. V37I突变的临床听力学特点[J]. 国际耳鼻咽喉头颈外科杂志, 2018, 42(6): 363-367.
[9] 张慧, 耿曼英, 单子丽, 等. 轻度感音神经性耳聋对婴幼儿言语能力发育的影响[J]. 中国实用神经疾病杂志, 2016, 19(13): 36-37.
[10] Pollak A, Skórka A, Mueller-Malesińska M, et al. M34T and V37I mutations in GJB2 associated hearing impairment: evidence for pathogenicity and reduced penetrance[J]. Am J Med Genet A, 2007, 143A(21): 2534-2543. doi: 10.1002/ajmg.a.31982
[11] Tsukada K, Nishio S, Usami S, et al. A large cohort study of GJB2 mutations in Japanese hearing loss patients[J]. Clin Genet, 2010, 78(5): 464-470. doi: 10.1111/j.1399-0004.2010.01407.x
[12] Wu CC, Tsai CH, Hung CC, et al. Newborn genetic screening for hearing impairment: a population-based longitudinal study[J]. Genet Med, 2017, 19(1): 6-12. doi: 10.1038/gim.2016.66
[13] Li L, Lu JR, Tao Z, et al. The p. V37I exclusive genotype of GJB2: a genetic risk-indicator of postnatal permanent childhood hearing impairment[J]. PLoS One, 2012, 7(5): e36621. doi: 10.1371/journal.pone.0036621
[14] Sakata A, Kashio A, Koyama M, et al. Hearing and hearing loss progression in patients with GJB2 gene mutations: a long-term follow-up[J]. Int J Mol Sci, 2023, 24(23): 16763. doi: 10.3390/ijms242316763
-
计量
- 文章访问数: 254
- 施引文献: 0