伴前庭水管扩大的非综合征性听力障碍耳聋基因突变谱研究

doi:10.3969/j.issn.1006-9771.2023.01.018

《中国康复理论与实践》 ›› 2023, Vol. 29 ›› Issue (1): 119-124.doi: 10.3969/j.issn.1006-9771.2023.01.018

• 应用研究 • 上一篇

伴前庭水管扩大的非综合征性听力障碍耳聋基因突变谱研究

王屹^1a^,², 陈振波^1b^,², 李勇³, 王晶俏^1a^,², 刘志忠^1a^,²()

1.中国康复研究中心北京博爱医院，a. 检验科；b. 影像科，北京市 100068
2.首都医科大学康复医学院，北京市 100068
3.中国医学科学院整形外科医院放射科，北京市 100144

收稿日期:2022-09-14 修回日期:2022-10-11 出版日期:2023-01-25 发布日期:2023-02-17
通讯作者: 刘志忠，男，博士，主任技师， E-mail： lzzlzb@126.com。
作者简介:王屹(1980-)，女，汉族，山西大同市人，博士，副主任医师，主要研究方向：耳基因检测在疾病防控中的应用研究、神经系统退行性疾病。

Deafness genetic mutation spectrum in nonsyndromic hearing impairment associated with enlarged vestibular aqueducts

WANG Yi^1a^,², CHEN Zhenbo^1b^,², LI Yong³, WANG Jingqiao^1a^,², LIU Zhizhong^1a^,²()

1. a. Department of Clinical Laboratory; b. Department of Radiology, Beijing Bo'ai Hospital, China Rehabilitation Research Center, Beijing 100068, China
2. Capital Medical University School of Rehabilitation Medicine, Beijing 100068, China
3. Department of Radiology, Plastic Surgery Hospital, Chinese Academy of Medical Sciences, Beijing 100144, China

Received:2022-09-14 Revised:2022-10-11 Published:2023-01-25 Online:2023-02-17
Contact: LIU Zhizhong, E-mail: lzzlzb@126.com

摘要/Abstract

摘要：

目的观察伴前庭水管扩大(EVA)的非综合征性听力障碍(NSHI)患者耳聋基因突变谱。

方法 2015年10月至2016年8月，对湖北宜昌特殊教育学校确诊为NSHI的患者85例进行颞骨CT检查，基质辅助激光解吸/电离飞行时间质谱对GJB2、GJB3、SLC26A4和线粒体DNA (mtDNA) 12S rRNA的20个耳聋相关基因突变位点进行检测。

结果颞骨CT显示EVA患者31例。与非EVA患者相比，EVA患者携带突变的比例明显增高(χ² = 11.160, P = 0.001)，主要表现为SLC26A4基因中c.919-2A>G突变水平显著增高(χ² = 23.870, P < 0.001)。

结论伴EVA的NSHI患者耳聋基因突变谱不同于非EVA患者，可优化耳聋基因检测方案，为伴EVA的NSHI的早诊断、早干预提供帮助。

关键词: 非综合征性听力障碍, 前庭水管扩大, 基因突变

Abstract:

Objective To investigate the deafness genetic mutation spectrum in nonsyndromic hearing impairment (NSHI) associated with enlarged vestibular aqueducts (EVA).

Methods From October, 2015 to August, 2016, 85 patients with NSHI from Hubei Yichang Special Education School were examined with temporal bone CT, and 20 deafness-related gene mutations in GJB2, GJB3, SLC26A4and mtDNA 12S rRNA were detected with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

Results A total of 31 patients were found EVA with temporal bone CT. Compared with non-EVA patients, the proportion of deafness-related gene mutations was more in patients with EVA (χ² = 11.160, P= 0.001), especially for c.919-2A>G mutation of SLC26A4 (χ² = 23.870, P< 0.001).

Conclusion The deafness gene mutation spectrum is different in NSHI patients with or without EVA. It is needed to optimize genetic testing scheme for deafness for early diagnosis and intervention of NSHI associated with EVA.

Key words: nonsyndromic hearing impairment, enlarged vestibular aqueducts, gene mutation

中图分类号:

R764.43

王屹, 陈振波, 李勇, 王晶俏, 刘志忠. 伴前庭水管扩大的非综合征性听力障碍耳聋基因突变谱研究[J]. 《中国康复理论与实践》, 2023, 29(1): 119-124.

WANG Yi, CHEN Zhenbo, LI Yong, WANG Jingqiao, LIU Zhizhong. Deafness genetic mutation spectrum in nonsyndromic hearing impairment associated with enlarged vestibular aqueducts[J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2023, 29(1): 119-124.

图/表 5

表1

各基因突变位点及引物序列"

基因	位点	正向引物	反向引物	延伸引物
GJB2	c.35delG	5'-ACG TTG GAT GGA AGT CTC CCT GTT CTG TCC-3'	5'-ACG TTG GAT GTT TGA TCT CCT CGA TGT CC-3'	5'-TTT GTT CAC ACC CCC-3'
	c.167delT	5'-ACG TTG GAT GGA AGT CTC CCT GTT CTG TCC-3'	5'-ACG TTG GAT GTT TGA TCT CCT CGA TGT CC-3'	5'-GAC TTT GTC TGC AAC ACC C-3'
	c.176_191del16	5'-ACG TTG GAT GGA AGT CTC CCT GTT CTG TCC-3'	5'-ACG TTG GAT GTT TGA TCT CCT CGA TGT CC-3'	5'-GGG GAA GTA GTG ATC GTA GC-3'
	c.235delC	5'-ACG TTG GAT GGA AGT CTC CCT GTT CTG TCC-3'	5'-ACG TTG GAT GTT TGA TCT CCT CGA TGT CC-3'	5'-CGA AGA TCA GCT GCA GG-3'
	c.299delAT	5'-ACG TTG GAT GGA AGT CTC CCT GTT CTG TCC-3'	5'-ACG TTG GAT GTT TGA TCT CCT CGA TGT CC-3'	5'-TGA ACT TCC TCT TCT TCT C-3'
GJB3	c.538C>T	5'-ACG TTG GAT GCC TCT TCC TCT ACC TGC TGC-3'	5'-ACG TTG GAT GCA CAG ATG GTG AGT ACG ATG C-3'	5'-TAG TGG ACT GCT ACA TTG CC-3'
	c.547G>A	5'-ACG TTG GAT GCC TCT TCC TCT ACC TGC TGC-3'	5'-ACG TTG GAT GCA CAG ATG GTG AGT ACG ATGC-3'	5'-TGA AGT AGG TGA AGA TTT TCT TCT-3'
SLC26A4	c.281C>T	5'-ACG TTG GAT GGA CTC TTG TGC CCA TCT TG-3'	5'-ACG TTG GAT GAT GGT AGC TGG GGA GAA GT-3'	5'-GGC CAC TAG CCC A-3'
	c.589G>A	5'-ACG TTG GAT GAA TGG AAC TGT ATT AAA TAC-3'	5'-ACG TTG GAT GTT GTA AGT TCA TTA CCT GT-3'	5'-CTT GTA AGT TCA TTA CCT GTA TAA TTC-3'
	c.919-2A>G	5'-ACG TTG GAT GAA GTT CAG CAT TAT TTG GTT GAC A-3'	5'-ACG TTG GAT GCC CCT TGG GAT GGA TTT AAC-3'	5'-GTA GTA GCA ATT ATC GTC-3'
	c.1174A>T	5'-ACG TTG GAT GTG AAA TAC TCA GCG AAG GT-3'	5'-ACG TTG GAT GCA TTC CTC GAC TTG TTC TC-3'	5'-GCC TTT GGG ATC AGC-3'
	c.1226G>A	5'-ACG TTG GAT GTG AAA TAC TCA GCG AAG GT-3'	5'-ACG TTG GAT GCA TTC CTC GAC TTG TTC TC-3'	5'-CAC CAC TGC TCT TTC CC-3'
	c.1229C>T	5'-ACG TTG GAT GTG AAA TAC TCA GCG AAG GT-3'	5'-ACG TTG GAT GCA TTC CTC GAC TTG TTC TC-3'	5'-TCC AGT GCT CTC CTG GAC GGC C-3'
	c.1707+5G>A	5'-ACG TTG GAT GTA ATG CCA GAT TGA AGA ACC-3'	5'-ACG TTG GAT GCA CAA AGG GAA GAG GGT CT-3'	5'-AAA ACA AAT TTC TAG GGA TAA AAT A-3'
	c.1975G>C	5'-ACG TTG GAT GTC CCA ACC AAG GAA ATA GA-3'	5'-ACG TTG GAT GTA CTG GAC AAC CCA CAT CA-3'	5'-CTC CAC AGT CAA GCA-3'
	c.2027T>A	5'-ACG TTG GAT GTC CCA ACC AAG GAA ATA GA-3'	5'-ACG TTG GAT GTA CTG GAC AAC CCA CAT CA-3'	5'-AGA ACC TTA CCA CCC GC-3'
	c.2162C>T	5'-ACG TTG GAT GGA AGA TTA TGT GAT AGA AAA G-3'	5'-ACG TTG GAT GTT TCT AAA ATG GAA CCT TG-3'	5'-TAC ACA TTC TTT TTG A-3'
	c.2168A>G	5'-ACG TTG GAT GGA AGA TTA TGT GAT AGA AAA G-3'	5'-ACG TTG GAT GTT TCT AAA ATG GAA CCT TG-3'	5'-CTG TAG ATA GAG TAT AGC ATC A-3'
mtDNA 12S rRNA	m.1494C>T	5'-ACG TTG GAT GTT AAG GGT CGA AGG TGG A-3'	5'-ACG TTG GAT GTA AGT TGG GTG CTT TGT G-3'	5'-CCT TTG AAG TAT ACT TGA GGA G-3'
mtDNA 12S rRNA	m.1555A>G	5'-ACG TTG GAT GTT AAG GGT CGA AGG TGG A-3'	5'-ACG TTG GAT GTA AGT TGG GTG CTT TGT G-3'	5'-ACT TAC CAT GTT ACG ACT TG-3'

表1

表2

表3

表4

表5

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组别	n	性别(男/女)/n	年龄/岁
EVA-NSHI	31	15/16	15.13±2.36
非EVA-NSHI	54	24/30	16.22±2.65
χ²/t值		0.123	19.04
P值		0.726	0.060

基因	等位基因1		等位基因2		n
基因	突变位点	结果/氨基酸变化	突变位点	结果/氨基酸变化	n
GJB2	c.235delC	移码	c.235delC	移码	4
	c.235delC	移码	c.299delAT	移码	2
	c.235delC	移码	野生型		1
SLC26A4	c.919-2A>G	异常剪接	c.919-2A>G	异常剪接	4
	c.2168A>G	p.H723R错义	c.2168A>G	p.H723R错义	1
	c.919-2A>G	异常剪接	c.2168A>G	p.His723Arg	2
	c.919-2A>G	异常剪接	c.1174A>T	p.Asn392Tyr	1
	c.919-2A>G	异常剪接	c.235delC (GJB2)	移码	1
	c.2168A>G	p.H723R错义	c.235delC (GJB2)	移码	1
	c.919-2A>G	异常剪接	野生型		4
	c.2168A>G	p.H723R错义	野生型		1
野生型	野生型		野生型		9

基因	等位基因1		等位基因2		n
基因	突变位点	结果/氨基酸变化	突变位点	结果/氨基酸变化	n
GJB2	c.235delC	移码	c.235delC	移码	10
	c.235delC	移码	c.299delAT	移码	3
	c.235delC	移码	野生型		3
	c.299delAT	移码	野生型		1
SLC26A4	c.919-2A>G	异常剪接	c.1707+5G>A	拼接区	1
	c.919-2A>G	异常剪接	野生型		1
	c.2168A>G	p.H723R错义	c.176_191del16 (GJB2)	p.Gly59AlafsTer18	1
	c.2168A>G	p.H723R错义	c.235delC* (GJB2)	移码	1
野生型	野生型		野生型		34

伴前庭水管扩大的非综合征性听力障碍耳聋基因突变谱研究

Deafness genetic mutation spectrum in nonsyndromic hearing impairment associated with enlarged vestibular aqueducts

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基因	突变位点	EVA-NSHI (n = 62)	非EVA-NSHI (n = 108)	χ²值	P值
GJB2	235delC	13	27	0.356	0.551
	299_300delAT	2	4	0.026	0.871
	176_191del16	0	1	—	—
	合计	15	32	0.582	0.446
SLC26A4	c.919-2A>G	16	2	23.870	< 0.001
	c.2168A>G	5	1	5.895	0.015
	c.1174A>T	1	0	—	—
	c.1707+5G>A	0	1	—	—
	合计	22	4	30.710	< 0.001
总突变		37	36	11.160	0.001

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