Study Of Relationship Between GJB2 Gene Mutation And Rehabilitation Of Auditory And Speech After Cochlear Implantation

Objective:To analyze the distribution of the inner ear malformation in patients with cochlear implantation,and to study the relationship between GJB2 gene mutation and inner ear malformation.To explore the feasibility of using the method of gene sequence analysis to help CT examination as diagnostic tool in patients with severe and profound sensorineural hearing loss.To analyze the effect of cochlear implantation on GJB2 mutation population,and to study the relationship between different mutation types and genotypes of GJB2 gene and the ability of auditory and speech after cochlear implantation.To explore the feasibility of GJB2 gene detection before operation to predict the efficacy of cochlear implantation.Methods:We collected the clinical data of patients with severe and profound sensorineural hearing loss who underwent cochlear implantation at the Department of Otorhinolaryngology of the Second Hospital Affiliated to Lanzhou University from2012 to 2018.Common deafness-related genetic tests were performed after the patients or their guardians signed the informed consent.After retrospective analysis of694 patients'temporal bone high-resolution CT,we classified the inner ear structure combined with Sennaroglu classification method.We further studied the relationship between GJB2 gene mutation and inner ear malformation.Assessment of auditory and speech ability was performed in patients with cochlear implantation.The methods of evaluation include aided threshold audiometry,CAP and SIR scales and open-set speech audiometry.We grouped our research subjects under five different criteria based on genetic test results:(1)GJB2 biallelic mutation group?GJB2 allelic mutation group and control group;(2)GJB2 homozygous mutation group?GJB2 compound heterozygous mutation group and control group;(3)three groups of the most common genotypes(c.235delC/c.235delC?c.235delC/c.299-300delAT and c.109G>A/wt)and control group;(4)genotype group of c.109G>A/wt?other mono-heterozygous mutation group and control group;(5)GJB2 gene mutation group and control group.Then we analyzed auditory and speech ability of each group under different assessment items.Results:1.Results of inner ear structure in patients with cochlear implantation:the normal inner ear structure accounts for 66.71%,and there are 231 cases with inner ear malformation with the rate of 33.29%.Three most common malformations are:EVA accounts for 18.59%,IP-?+EVA accounts for 8.50%and IP-?accounts for 2.02%.The other malformation is 4.18%.2.Results of classification of inner ear malformation:three most common malformations are:EVA accounts for 55.84%,IP-?+EVA accounts for 25.54%and IP-?accounts for 6.06%.The other malformation is 12.55%,including IP-??IP-??CH?CC?internal auditory canal stenosis?enlarged internal auditory canal?semicircular canal dysplasia.Among 231 patients with inner ear malformation,212are symmetrical,19 are asymmetrical.Among patients with asymmetric binaural deformities,7cases are monaural and 12 are binaural deformities but asymmetrical.3.Relationship between GJB2 gene mutation and inner ear malformation:GJB2gene mutation accounts for 6.93%in the inner ear malformations and 25.49%in the normal inner ear structure,and there is a statistical difference(x~2=34.072,P<0.001).There are no statistical differences of the distribution of GJB2 biallelic mutation group?allelic mutation group and control group in the inner ear malformation group and normal inner ear structure group,respectively(x~2=5.283,P=0.071).Among 134patients with GJB2 gene mutations,16 cases have inner ear malformations(11.94%),118 cases have normal inner ear structure(88.06%).There are no statistical differences of the distribution of inner ear malformations in the GJB2 biallelic mutation group?allelic mutation group and control group(x~2=3.658,P=0.161).There is a statistically significant difference in the results of genetic mutations in the binaural symmetric deformities group and the asymmetric binaural deformities group(x~2=15.147,P<0.001).4.Distribution of GJB2 gene mutation types and genotypes:there are 11 hot mutation sites detected,the quiet common are:c.235delC?c.299-300delAT and c.109G>A with the detection rates of 65.08%?36.51%and 17.46%,respectively.A total of 18 genotypes are detected in 63 patients with GJB2 gene mutation.The three most common genotypes are:c.235delC/c.235delC?c.235delC/c.299-300delAT and c.109G>A/wt,accounting for 25.40%?23.81%and 15.87%,respectively.5.Results of evaluation of rehabilitation of auditory and speech ability:there are no significant differences in gender,ethnicity,the side of using CI and listening mode between GJB2 gene mutation group and control group(P>0.05).There is no statistical difference in implantation age between groups after grouping under each standard.Aided hearing threshold:a total of 215 patients with CI completed hearing threshold assessment.The hearing thresholds of the GJB2 gene mutation group at several frequencies are higher than that of control group.There are no statistical differences of hearing threshold and average threshold in three genotype groups.The hearing threshold of the genotype group of c.109G>A/wt is higher.CAP and SIR scales:a total of 223 patients with CI completed CAP and SIR assessment.There are no statistical differences of CAP and SIR scores between groups after grouping under each standard.Open-set speech audiometry:there are no statistical differences in monosyllabic words?spondee words?sentences in quiet condition and sentences in noise condition with a SNR+10dB between groups after grouping under each standard.Conclusions:1.The incidence of inner ear malformation in the cochlear implant population is33.29%.Three most common malformations are:EVA,IP-?+EVA and IP-?.2.Inner ear malformation is not clearly associated with GJB2 gene mutation and it's genotype.GJB2 gene mutation is not a determining factor for inner ear malformation.3.Distribution of GJB2 gene mutation types and genotypes:the three most common hot mutation sites are:c.235delC?c.299-300delAT and c.109G>A.The three most common genotypes are:c.235delC/c.235delC?c.235delC/c.299-300delAT and c.109G>A/wt.4.Different alleles,different genotypes of GJB2 gene have the same effects in auditory and speech rehabilitation as patients without mutations.Patients with GJB2gene mutation can obtain stable auditory and speech rehabilitation after cochlear implantation.5.Cochlear implantation is effective for hearing and speech rehabilitation in patients with hearing loss related to GJB2 gene mutation.The detection of GJB2 gene mutation can be an effective predictor of molecular etiology for CI surgery in patients with bilateral severe to profound sensorineural hearing loss within 7 years.