Analysis Of Deafness Genes Mutation In Shijiazhuang And Surrounding Areas And Identification Of A Novel Mutation Of NOG In Family With Syndrome Hearing Impairment

Part ? Analysis of deafness genes mutation in Shijiazhuang and surrounding areasObjectives By analyzing the genes mutation of hereditary deafness in the population of Shijiazhuang and surrounding areas,we understood the genes mutation spectrum and frequency of common hereditary deafness in the area,laid the theoretical basis for the prevention and diagnosis of hereditary deafness in the population.Methods 51 non-syndrome hearing impairment(NSHI)patients and 299 normal hearing patients were selected from Shijiazhuang and surrounding area,who sought medical advice to Hebei Provincial People's Hospital for voluntary deafness gene screening.We extracted the genomic DNA from blood cells and performed the PCR amplification,then we detected 15 deafness mutation sites in four deafness-related genes of GJB2,SLC26A4,GJB3 and mtDNA12SrRNA in genomic DNA by using genetic deafness gene chip.Finally,statistical software was used to analyze the mutations.Results Among the 51 NSHI patients,17 cases gene mutations were detected,accounting for 33.33%.The detection rate is arranged in order from high to low:GJB2,SLC26A4,GJB3 and mtDNA12SrRNA.There were 8 cases of GJB2 mutations,accounting for 15.69%,6 cases of GJB2 235de1C mutation,and 2 cases of GJB2 299-300delAT combines 235de1C compound heterozygous mutation.There were 7 cases of SLC26A4 gene mutation,accounting for 13.73%,1 case of 2168A>G heterozygous mutation,5 cases of SLC26A4 IVS7-2A>G mutation,and 1 case of SLC26A4 IVS7-2A>G and 1229C>T compound heterozygous mutations.1 case of GJB3 538C>T,accounting for 1.96%.MtDNA12SrRNA 1555A>G homogenous mutation was found in 1 case,accounting for 1.96%.Among 299 cases with normal hearing,28 cases(9.36%)were detected.GJB2 gene was detected in 8 cases,accounting for 2.68%,including 5 cases of GJB2 235de1C heterozygous mutation,2 cases of GJB2 299-300delat heterozygous mutation,and 1 case of GJB2 299-300delat and 235de1C compound heterozygous mutations.SLC26A4 gene mutation was detected in 14 cases,accounting for 4.68%,including 4 cases of SLC26A4 2168A>G heterozygous mutation,6 cases of SLC26A4 IVS7-2A>G mutation,1 case of SLC26A4 1229C>T heterozygous mutation,2 cases of SLC26A4 1174A>T heterozygous mutation,and 1 case of SLC26A4 2168A>G combined with IVS7-2A>G heterozygous mutations.GJB3 538C>T heterozygous mutation in 6 cases.Among the 22 cases in the high-risk factors group,7 cases(31.82%)were detected.GJB2 gene was detected in 1 cases.The mutations of SLC26A4 gene were detected in 4 cases.GJB3 gene mutations were detected in 2 cases.Among 277 cases in the low-risk group,21 cases(7.58%)were detected.GJB2 detected in 7 cases,SLC26A4 mutations detected in 10 cases,GJB3 detected 4 in cases.Genetic mutations were detected in 10(33.33%)cases with congenital deafness(n=30)and 7 cases(33.33%)with acquired deafness(n=21).Through statistical analysis,The rate of deafness gene detection was statistically different between the deafness group and the normal hearing group(P<0.001).The detection rate of deafness genes in high risk group and non-high risk group was statistically different(P<0.001).There was no significant difference in the detection rate of congenital deafness and acquired deafness group(P>0.05).Conclusions 1.GJB2 and SLC26A4 are the main genes for deafness in Shijiazhuang and surrounding areas.2.The detection rate of the group with high risk of deafness genes mutation was significantly higher than the group without high risk in the normal hearing population,which indicated that hearing normal people with high risk factors are still the focus of genetic screening for deafness.3.Patients with congenital deafness and acquired deafness are advised to perform genetic testing and genetic counseling for deafness.Figure[1];Table[5];Reference[27]Part ? Identification of a novel mutation of NOG in family with syndrome hearing impairmentObjectives In this study,genetic methods were used to analyze the genetic pathogenic genes and mutation sites of the SYM1A families,determined the pathogenic factors of the family,and provided genetic counseling and prenatal diagnosis.Methods After gathered the family's clinical medical records and drew the family tree map,we extracted peripheral blood samples and genomic DNA.And by filtering in the dbSNP,1000G,Ex AC,and GenomAD Database to obtain the pathogenic mutation sites.Co-separation was performed using Sanger sequencing method,and the frequency of the mutation site was screened in 200 normal controls.In the end,bioinformatics softwares were used to predict and analyze the structure and function of the protein.Through these processes,the mutation site of the pathogenic gene was identified.Results 1.We revealed a new NOG gene c.690C>G(p.C230W)in the proximal symphalangism syndrome with deafness family.2.Sanger sequencing of amniotic fluid cells revealed that the fetus did not carry the pathogenic gene.Conclusions The disease-causing gene of the proximal symphalangism syndrome with deafness family was the NOG gene mutation site:c.690C>G(p.C230W).This mutation site was discovered and reported for the first time.Figure[9];Table[2];Reference[15].