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

Abstract

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

CLC Number:

R764.43

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.

Figures/Tables 5

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'

References 34

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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

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

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

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