Correlation Analysis Of Deafness Gene Detection And Curative Effect In 43 Cochlear Implant Patients And Deafness Family Study

PartⅠ Detection of deafness genes in 43 cochlear implant patients and analysis of their correlation with curative effectObjective:Detecting deafness genes in 43 patients with cochlear implants(CI)and researching the deafness mutations in southern Sichuan.Analyzing the speech and hearing rehabilitation after CI implantation to research the efficacy of CI implantation,and analyzing correlation between gene mutation types and the rehabilitation effect after cochlear implantation.Method:Retrospective analysis of clinical data of 43 deaf patients who underwent CI implantation at the Department of Otorhinolaryngology Head and Neck Surgery at at the Affiliated Hospital of Southwest Medical University from October 2017 to June 2018,including detailed medical history,signs,audiology and imaging examination data.Peripheral blood of 43 patients was collected for gene testing,the detection sites were all GJB2 sequences,SLC26A4IVS7-2A>G,1079C>T,1174A>T,1226G>A,1229C>T,2168A>G,mt DNA12 Sr RNA1555A>G,1494C>T.The patients were divided into two groups:patients with disease-casuing mulation were classified as group A;and those without mutations as group B.Unilateral cochlear implants were performed in all patients of both groups.Their classification of auditory performance(CAP)and speech intelligibility rating(SIR)were evaluated before operation and at 3,6 and 12 months after surgery.Analyze the relationship between genetic results and clinical efficacy.Results :There were 14 cases(group A)with a positive rate and 29 with a negative rate(group B)in 43 patients.During 14 patients 9 cases were positive for GJB2(20.93%),235 del C was main mulation;6 cases for SLC26A4(13.95%),IVS7-2A>G was main mulation,and 1 patient was GJB2176del16,SLC26A4IVS7-2A>G,1079C>T complex heterozygous mutation during them;none for mt DNA12 Sr RNA mulation.Imaging studies found 5patients had large vestibular aqueduct syndrome(LVAS),of which 4 had Mondini deformity(IP type II).Of the 5 LVAS patients,4 were positive for SLC26A4 and 1 was negative.One patient had internal auditory canal stenosis.Rehabilitation effect:the CAP and SIR scores of both groups were significantly improved at different time points within 1 year after operation,the scores gradually increased with the prolongation of postoperative time(P<0.05).But the differences of both CAP and SIR scores between the two groups at all time points were statistically insignificant(all P>0.05).Conclusion :The common gene mutation in 43 deafness patients in South Sichuan are GJB2 and SLC26A4,235 del C and IVS7-2A>G were tthe most common mutation sites.Cochlear implantation can effectively improve the hearing and speech ability of the patients.But the above two types of deafness mutations have no significant correlation with postoperative recovery.Part II Study on pathogenic genes of deafness in three deafness familiesObjective : To explore the causes of deafness of probands and the relationship between deafness genotypes and parental genotypes.Methods:The clinical data of 43 children were retrospectively analyzed.Three families were selected as the research objects,blood samples were collected from patients and their parents,GJB2,SLC26A4 and mt DNA12 Sr RNA gene screening were performed.Next generation sequencing of 139 deafness genes and 6 common mitochondrial drug-induced deafness sites was performed in a family(family 1)in which patient’s were not found pathogenic gene in three genes and his brother was also deafness.Related softwares and databases analysis results,Sanger sequencing verification them.Screening of the above three genes revealed that the genotypes of the proband were GJB2 235 del C homozygous mutation,SLC26A4IVS7-2A>G,1079C>T complex heterozygous mutation(family 2,family 3),and one generation sequencing of these two families verified the corresponding loci of their parents.Results:The base substitutions in the 349 and 908 positions of the HARS2 gene coding region in 2 patients of the sequenced family 1 were both HARS2 349G>A,908T>C complex heterozygous mutations,which were the main cause of deafness in 2 patients.Sanger sequencing confirmed that the father carried a 908T>C heterozygous mutation and the mother carried a 349G>A single heterozygous mutation.The proband of pedigree 2 was a homozygous mutation of GJB2 235 del,GJB2 235 del single heterozygous mutation of father and mother.The proband of family 3 was SLC26A4 IVS7-2A>G,1079C>T complex heterozygous mutation,father SLC26A4 1079C>T single heterozygous mutation,and mother SLC26A4 IVS7-2A>G single heterozygous mutation.Conclusion :Deafness was caused by HARS2 349G> A,908T> C complex heterozygote in 2 patients in family 1,it was also speculated that the mutation might cause Perrault syndrome(PRLTS)in 2 patients to manifest SNHL.The parents of the probands in the 3 pedigrees had normal hearing and all carried a single mutation site,the patients who had acquired the deafness genes from their parents performed deafness,their genotype were homozygous mutations or complex heterozygous mutations.Next generation sequencing technology is an important method for discovering new deafness pathogenic sites.Deafness gene detection is important for patients with a family history of hereditary deafness to guide marriage and childbirth to avoid the next generation of deafness genes.