Exome Sequencing Of 10 Cases Of Congenital Deafness In Inner Mongolia Autonomous Region Sequencing And Analysis

Objective Objective congenital deafness is one of the most common birth defects in human beings.Whether the cause of deafness is hereditary,whether it is safe to procreate or reproduce is an urgent concern for deaf patients and their families.A large number of inherited causes of deafness remain unknown,and most mutations are extremely rare and have been reported in only one or a few families.Therefore,in order to further clarify the genetic etiology of deafness population in Inner Mongolia autonomous region.The whole exome sequencing of 10 patients with congenital deafness in the people's hospital of Inner Mongolia autonomous region was performed to further improve the genetic database of Inner Mongolia,so as to provide a basis for the early diagnosis,treatment and prenatal screening of deafness patients in the future.Methods 10 blood samples were randomly selected from the deafness sample bank of the people's hospital of the Inner Mongolia autonomous region(currently there are nearly 1000 blood samples of children with deafness in the deafness sample bank of the people's hospital of the Inner Mongolia autonomous region,which are kept in the refrigerator at-80 ?,and each sample has signed an informed consent with its parents or guardians).They were all patients with congenital sensorineural deafness.Complete exome sequencing was performed.Implement data quality control through Fast QC software.High-quality Reads were compared with reference genomes.NCBI db SNP database,Hapmap8 SNP data set,1000 Genomes,Yan Huang(YH)were used for screening and analysis of SNPs database,and the variation of each sample was compared with each database to screen out gene variation related to deafness.Results 1.6 of the 10 patients with non-syndromic deafness had genemutation,and the detection rate was 60%(6/10).2.Three patients(30%)with GJB2 gene mutation had the highest detection rate.Among them,there were 2 cases with pure sum mutation of 235 del C and 1 case with complex heterozygous mutation of235 del C/ 299-300 delat,and the detection rate was 10%(1/10).3.The mutation of SLC26A4 gene with the second highest detection rate was 20%(2/10),both of which were pure sum mutations of ivs7-2a > G.4.1 case was detected Col1a1/Col1a2 gene mutation.5.There was no statistical difference in the mutation rate of GJB2 gene between Inner Mongolia autonomous region and other provinces and cities(P =0.702,P = 0.378).There was no statistical difference between the average level of GJB2(pure and mutation of 235 del C locus,complex heterozygous mutation of235 del C/ 299-300delat)and that of other 18 provinces and cities in China(P values were 0.166 and 0.286,respectively).There was no statistical difference between SLC26A4(ivs7-2a > G locus with mutation)and the average level of other 27 provinces and cities in China(P value was 0.376).There was no statistical difference in mutation rates of GJB2 and SLC26A4 between han and Mongolian(P=1.000).There was no statistical difference in mutation rates of GJB2 and SLC26A4 genes between males and females(P=1.000).There was no statistical difference in the mutation rate of GJB2(pure sum mutation of 235 del C locus)gene locus between han and Mongolian in our region(P=1.000).There was no statistical difference in the mutation rate of SLC26A4(ivs7-2a > G locus pure and mutation)between han and Mongolian in our region(P=1.000).There was a statistical difference between the detection rate of pathogenic mutations by whole-exome sequencing and first-generation sequencing(P=0.01),and the detection rate of pathogenic mutations by whole-exome sequencing was higher than that by first-generation sequencing.Conclusion GJB2 and SLC26A4 are the most common deaf-causing genes in patients with non-syndromal deafness in Inner Mongolia autonomous region,which further confirms the previous study.There is no significant difference between the results of other regions in China,and there is no significant difference between the han nationality and Mongolian nationality,or between males and females.Thisexperiment detected 1 case of Col1a1 / Col1a2 gene mutations,although Col1a1 /Col1a2 gene mutations in the multiple literature reports related to the occurrence of otosclerosis,but through this article analysis,otosclerosis can not cause congenital severe-extremely severe sensorineural deafness,so consider it is not only the causes of congenital sensorineural deafness.Moreover,the gene Col1a1/Col1a2 will affect collagen synthesis,and collagen is expressed in multiple parts of the inner ear.Considering that the mutation of the gene Col1a1/Col1a2 will cause lesions in multiple parts of the inner ear,resulting in congenital sensorineural deafness.