Screening Analysis Of Common Hereditary Deafness Gene Mutation In High Risk Individuals Of Changchun

Objective:By screening common hereditary deafness gene mutation in high risk individuals of Changchun,Jilin Province,to find out the hot spot mutation site and mutation frequency in this area,and to give corresponding fertility guidance and suggestions to grope for the prevention and treatment strategies for reducing the birth rate of deaf patients in this area.Method:After informed consent,the high-risk individuals of hereditary deafness and normal individuals in Changchun were collected to set up as high-risk group and control group respectively.There were 109 cases in high risk group and 40 cases in control group.In the high-risk group,there were 71 cases of deafness who were moderately or severely sensorineural deafness and 38 cases with normal hearing whose close relatives within three generations has a history of deafness(most of them were families of the patients mentioned above).The individuals of control group had normal hearing and no family history of deafness.The related history was collected,and examination was carried out.After blood collection,the DNA was extracted and amplified.And then 15 hot spot mutation sites on four deafness related genes were detected with gene chip.The including genes and sites were: GJB2(35 del G,176 del 16,235 delC,299 delAT),SLC26A4(IVS7-2A>G,2168A>G,1174 A>T,1226 G>A,1229 C>T,1975 G>C,2027 T>A,IVS15+5 G>A),mitochondrial 12 S rRNA(1494C>T,1555A>G)and GJB3(538C>T).Microarray scanner was used to scan and identify the deafness genes.For those who were detected to carry mutation genes or sites,explanations and suggestions were provided for them.Finally,statistics and analysis were made on the data.Result:There were 40 cases in the control group,and 2 cases were positive,the detection rate was 5%(2 / 40).One of them carried SLC26A4 heterozygous mutation,and the other carried both GJB2 and SLC26A4 heterozygous mutations.There were 109 cases in high risk group,including 71 deaf patients and 38 normal hearing patients,accounting for 65.1% and 34.9% respectively.43 cases were detected positive in high risk group,the total positive rate was 39.4%.The detection rate of deafness group was 45.1%(32 / 71).Among them,there were 12 cases(16.9%)of GJB2 gene mutation: 7 cases of 235 delc homozygous mutation,2 cases of 235 delc and 299 del AT compound heterozygous mutation,and 3 cases had 235 delc heterozygous mutation;There were 20 cases of SLC26A4 mutations(28.1%): 3 cases of IVS7-2A > G homozygous mutation,1 case of IVS7-2A > G and 1229C>T compound heterozygous mutations,1 case of IVS7-2A > G and 2168A>G compound heterozygous mutations,10 cases of IVS7-2A > G heterozygous mutation,2 cases of 2168A>G heterozygous mutation,2 cases of 2027T> A heterozygous mutation and 1 case of 1226 G>Aheterozygous mutation;There were 4 cases of mitochondrial gene mutation(5.6%): 2 cases of 1555 A > G homozygous mutation(2.8%),2 cases of 1494 c > t homozygous mutation(2.8%);And there were 1 case(1.4%)of GJB3 gene mutation,which was 538 c > t heterozygous mutation.In the high risk group,the detection rate of the subjects with normal hearing were 28.9%(11 / 38),all of whom were heterozygous.Among them,there were 4 cases of GJB2 gene mutation(10.5%),7 cases of SLC26A4 gene mutation(18.4%)and mitochondrial gene mutation in 1 case(2.6%).The total detection rate of high risk group was significantly higher than that of control group(P < 0.05).The detection rate of GJB2 and SLC26A4 gene mutation in high-risk group was also significantly higher than that in the control group(P < 0.05).Although the detection rate of GJB3 and 12 S RNA was higher than that in the control group,but there was no statistical significance(P > 0.05).The detection rate of each gene mutations in deaf patients was higher than that in normal hearing patients,but there was no statistical significance(P > 0.05).In the high-risk group,19 families(49 cases)were examined,4 of them(11 cases)had deafness genes,accounting for 21.1%(4/19);38 cases in 15 families were detected of no deafness gene mutation or could not explain the reason of deafness.Conclusion:1.The gene mutation carrying rate of the high risk population of hereditary deafness in Changchun area is much higher than that of the normal population.2.In this study,the most common mutations of deafness genes in Changchun are SLC26A4 and GJB2,and the detection rate of SLC26A4 gene is at a high level in China.235 delC of GJB2 and IVS7-2A > G of SLC26A4 are the hot spot mutations in Changchun.