Analysis Of Deafness Genes’ Mutation In Deaf Children In Shenzhen Area

Objective: GJB2,SLC26A4 and mt DNA12 Sr RNA are the most common deaf genes in China.In some areas,there is still a lack of deafness gene mutation analysis for deaf children.This study conducted statistics on deafness-related gene mutations in deaf children in Shenzhen,summarized the rules of the mutant deafness genes and mutation types,and analyzed the hot deafness genes,hotspot mutations and detection frequency of deaf children in the region.Methods: We selected 92 children with hearing loss and deafness gene mutation diagnosed in the Otolaryngology Clinic of Shenzhen Children’s Hospital from March2013 to April 2019,and counted their basic data,deafness characteristics,family status,and history of aminoglycoside drugs,Imaging examination results,using high-throughput sequencing technology to detect 406 deaf-related genes in 92 cases of deaf children.At the same time,sanger sequencing was used to detect the relevant mutation sites of the parents of the children,and the source of the mutation was identified as hereditary or spontaneous.Finally,the statistics Hot-spot deafness genes,hot-spot mutations and detection frequency in children with deafness in the region.Results: 1.92 cases of deaf children were screened out,all of Han nationality,registered in Shenzhen,males(47 cases)and females(45 cases)had little difference in the number of genders,and the age of onset of children under 3 years old(84/92,91.30%)was significantly more than that Children with onset after 3 years of age(8/92,8.70%),non-progressive hearing loss(69/92,75.00%)are more common than progressive children(8/92,8.70%),and sporadic cases(89/92,96.74%),Accounting for more than family cases(3/92,3.26%).The deaf children included in this study are mainly pre-lingual deafness(onset before 3 years old),non-progressive deafness and sporadic cases.2.Through high-throughput sequencing,it was found that the top three deafness genes with mutation carrier rates in deaf children in Shenzhen were PCDH15(25/92,27.17%),GJB2(23/92,25.00%),and USH2A(22/92,23.91%).Among the 25 children with PCDH15 gene mutations,19 PCDH15 mutation types were detected.The types of mutations were varied,and no typical hot spot mutations were found.Among 23 children with mutations in the GJB2 gene,4 types of mutations were found,among which the detection rates of 2 hotspot mutations were c.109G>A(28/184,15.22%,)and c.235 del C(7/184,3.80%),it can be seen that the detection rate of c.109G>A mutation is significantly higher than other sites.Among 22 children with USH2 A gene mutations,25 types of USH2 A mutations were found,and no typical hot spot mutations were seen.Statistics show that the top three common deafness gene mutation types in deaf children in Shenzhen are GJB2 c.109G>A(28/184,15.22%),GJB2 c.235 del C(7/184,3.80%),SLC26A4 919-2A>G(5/184,2.72%).3.Among 92 deaf children in Shenzhen,13 cases of homozygous mutation were found,of which 10 cases were GJB2 homozygous mutation(10/14,71.4%),of which 8 cases were GJB2 c.109G>A homozygous mutation,and GJB2 c.235 del C was pure There were2 cases of homozygous mutations,and the other homozygous mutations were SLC26A4(c.919-2A>G),MYO7A(c.6028G>A)and MPZL2(c.220C>T).Forty children with compound heterozygous mutations,the most common compound heterozygous mutation gene was USH2A(6/40,15.00%).Two of the children had 3 different USH2 A gene mutations,and no typical common mutation types were found.4.After high-throughput sequencing of 92 deaf children in Shenzhen area,the deafness gene was detected in 10 children(10.87%)with pathogenic mutations,of which 3 cases were spontaneous mutations,5 cases of mutations originated from parents,and 2 cases of mutation originated from fathers.Suspected pathogenic mutations were found in 30cases(32.61%),and no related pathogenic mutations were found in 52 cases(56.52%).Conclusion: The deaf genes with the highest mutation rates in deaf children in Shenzhen are PCDH15,GJB2,USH2 A,and the hotspot mutations are GJB2 c.109G>A,GJB2 c.235del C,SLC26A4 c.919-2A>G,respectively.The hotspot mutations in this region are concentrated in GJB2 and SLC26A4,and the detection frequency of GJB2 c.109G>A is much higher than other mutation types.