| Objective:To study the molecular epidemiology of cochlear implant recipients with nonsyndromic hearing loss,and to investigate the distribution and hot spot mutation of the four genes in cochlear implant patients with non-syndromic hearing loss.To study the molecular epidemiology of cochlear implant recipients with nonsyndromic hearing loss,and to investigate the distribution and hot spot mutation of the four genes in cochlear implant patients with non-syndromic hearing loss.Methods:A total of 398 cochlear implant recipients from the Department of ENT of Lanzhou University Second Hospital from 2012 to 2015 were included in this study.After obtaining informed consent from all patients or their parents,5–10 ml peripheral venous blood of all patients was drawn to extract genomic DNA.SNPscan method was used to screen for GJB2 gene,GJB3 gene,SLC26A4 gene and m.DNA1555A>G,m.DNA1494C>T and m.DNA1095T>C mutations.With reference to the latest international classification standards[1],retrospective analysis of the sample's imaging data and correlation analysis with genetic results were carried out.Results:1.The 398 cochlear implant recipients?n=398?with nonsyndromic hearing impairment were composed of 207 male and 191 female,with a male to female ratio of1:0.92.Among them,334 were Han,43 were Hui,10 were Tibetan and 10 were Dongxiang nationality.There were 50 cases had a family history of deafness and 358were prelingual deafness?average age:5.00±3.28 years old?,accounting for 12.56%of all cases?50/398?and 89.95%?358/398?respectively.2.In the 398 patients 108 were proven carrying GJB2 gene mutations,accounting for 27.13%of all cases?108/398?.The detected mutations composed of 39heterozygous,39 compound heterozygous,and 36 homozygous mutations.And the three most common pathogenic mutations were c.235delC,c.109G>A and c.299300delAT.The allele frequencies were 12.31%,3.38%,and 3.89%,respectively.A total of 23 genotypes of GJB2 gene were found,among them,[c.235delC]/[235delC],[c.109G>A]and[c.235delC]/[c.299300delAT]were the three most common types,accounting for 28.70%?31/108?,23.15%?25/108?and 15.74%?17/108?respectively.They accounted for 67.59%?73/108?of all genotypes.3.Eight of the included patients in the study carried GJB3 mutations,which were all heterozygous,accounting for 2.01%of all cases?8/398?.Among them,seven were c.580G>A and one was c.538C>T mutation,and the allele frequencies were 0.88%and0.13%,respectively.4.A total of 83 cases with SLC26A4 gene mutations were found in the 398 cases of cochlear implantation,accounting for 20.85%of all cases?83/398?.There were 20heterozygous,23 homozygous and 40 compound heterozygous mutations.The three most common mutations were c.919-2A>G,c.2168A>G and c.1229C>T with allele frequencies of 9.17%,2.25%and 0.75%,respectively.Among the 41 detected genotypes of SLC26A4 gene,the most five common were[c.919-2A>G]/[c.919-2A>G],[c.919-2A>G]/[c.2168A>G],[c.1174A>T]/[c.2168A>G],[c.1489G>A]and[c.919-2A>G]/[c.1229C>T].which accounted for 24.10%?20/83?,9.64%?8/83?,8.43%?7/83?,3.61%?3/83?and 3.61%?3/83?,respectively.The five genotypes accounted for 53.01%of all genotypes.5.Among the 398 cochlear implant recipients enrolled in this study,nine patients were shown to have m.1555A>G or m.1095T>C mutation,accounting for 2.26%of all cases.m.1555A>G and m.1095 T>C were found in five and four cases,respectively.6.No mutation of the GJB2,GJB3 and SLC26A4 gene or m.1555A>G,m.1494C>T and m.1095T>C was found in 199 patients of the 398 cochlear implants recipients,accounting for 50%of the total cases.7.Among the 398 cochlear implant patients,there were 137 cases of inner ear malformation with the rate of 34.42%?137/398?.There were 132 bilateral cases with the rate of 96.35%?132/137?,and 5 unilateral cases with the rate of 3.64%?5/137?.269ears were involved,155 ears were suffered with enlarged vestibular aqueduct with the rate of 57.62%?155/269?.11 ears were suffered with Vestibular and semicircular deformity with the rate of 4.89%?11/269?.2 ears were suffered with internal auditory canal stenosis with the rate of 0.74%?2/269?.5 ears were suffered with Internal auditory canal expansion with the rate of 1.86%?5/269?.There were 96 ears of cochlear malformation with the rate of 35.68%?96/269?.Cochlear dysplasia type II was found in 2 ears with the rate of 2.08%?2/96?,the rate of type III cochlear dysplasia was4.17%?4/96?.The rate of type I incomplete separation was 38%?9/96?,the rate of type II incomplete separation was 76.04%?73/96?,the rate of type III incomplete separation was 5.21%?5/96?.222 ears were suffered with enlarged vestibular aqueduct accounting for 82.52%?222/269?.8.Patients were divided into no deformity group and deformity group,the detection rate?32.95%?and allele frequency?26.82%?of the GJB2 gene in the non-deformities group were all higher than those in the deformity group?15.33%,12.41%?.The incidences of inner ear malformations in single allele mutation group,biallelic mutation group,and negative group of GJB2 gene are 20.00%?8/40?,19.11%?13/68?and 21.60%?43/199?,respectively.There was no statistical difference between the three groups.9.Grouped according to whether there is vestibular aqueduct enlargement,the frequency of SLC26A4 mutation allele was 1.15%in the group without inner ear malformation,and the frequency of SLC26A4 mutation allele in EVA group was 59.91%,and they had a statistically significant difference?p<0.05?;The frequency of SLC26A4mutation allele in inner ear malformations without the vestibular aqueduct enlargement group was 2.50%,which was statistically different from the EVA-related group?p<0.05?.And the SLC26A4 gene compound heterozygous mutation or homozygous mutation in 63 cases,the corresponding cases were vestibular aqueduct related patients,the consistency was 100%.10.The allele frequencies of SLC26A4 with no vestibular aqueduct?3.13%?and no obvious inner ear malformation?1.15%?were compared,and there was no significant statistical difference.Compared the vestibular aqueduct?3.13%?and the vestibular aqueduct related malformation?59.10%?,which had a statistical difference.Conclusion:1.Among the 398 cochlear implant recipients with nonsyndromic severe hearing loss,108 cases had GJB2 gene mutation,accounting for 27.13%?108/398?;8 cases had GJB3 gene mutation,accounting for 2.01%?8/398?;83 cases had SLC26A4 gene mutation,accounting for 20.85%?83/398?,and mutations in the mitochondrial m.1555A>G or m.1095T>C mutations were found in 9 cases,accounting for2.26%?9/398?.A total of 50%of the total cases.2.A total of 147 cases of molecular etiology were identified,accounting for 36.94%?147/398?.In detail,75 cases with GJB2 biallelic alleles,63 cases with SLC26A4biallelic alleles,and 9 cases with m.1555A>G or m.1095T>C mutation were detected.However,the molecular etiology of the remaining 251 cases,accounting for 63.06%?251/398?of the total cases remained unclear.3.The incidence of internal ear malformation in the patients with non-syndromic profound sensorineural deafness was about 33.79%.The most common type was enlarged vestibular aqueduct with the rate of 57.62%?155/269?.The incomplete division of the II type is the secondary type,with the rate of 35.68%?96/269?.4.Mutation of GJB2 gene is not an important factor of inner ear malformation.5.Mutation of SLC26A4 gene is the main pathogenic factor of vestibular aqueduct associated malformation and incomplete segregation?type II?.6.SLC26A4 gene mutation was not associated with non-vestibular aqueduct associated malformation. |
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