Analysis The Prevalence Of Deafness Genes In Cochlear Implantation Patients And Their Family Members

Chapter 2(section 2)Prevalence of the GJB2 gene mutation in 330 Jiangsu Cochlear Implant PatientsIntroduction:GJB2 gene mutations are highly prevalent in pre-lingual hearing loss patients from China.Pre-lingual deafness is a sensorineural disorder that can only be treated with cochlear implantation(CI).Materials and methods:The prevalence of GJB2 gene mutations was examined in 330 randomly selected patients with cochlear implantation.And 462 normal-hearing individuals were gathered for control.Results:Overall,276(83.64 per cent)patients carried variations in the GJB2 gene.Seventeen diefferent genotypes were identified,including 10 confirmed pathogenic mutations(c.235delC,c.299delAT,c.176del16,p.E47X,p.T123N,p.V167M,P.C218Y,p.T86R,p.V63L,p.R184Q),three polymorphisms(p.V27I,p.E114G,p.I203T),and two unidentified mutations(p.V37I,c.571T>C).Conclusions:A total of 103(31.2 per cent)patients carried two confirmed pathogenic mutations.The frequency of c.235del C was higher than that reported previously in Jiangsu province.The two novel mutations identified,69C>G and 501G>A,are likely to be polymorphisms.Chapter 3(section 3)GJB2 mutations in Sensorineural Hearing Loss children with Pediatric Inguinal HerniasIntroduction:Sensorineural hearing loss is still the most common birth defect worldwide.There are about 10%-30%congenital sensorineural hearing loss patients carry the GJB2 mutation in China.Inguinal hernia is the commonest pediatric surgical disease,the prevalence rates estimated from 0.8 to 4%in Taiwan children.Genetic factors have been investigated as a vital risk factor for hernia,and the hepatocyte growth factor(HGF)gene is also associated with nonsyndromic hearing loss.The HGF gene as a neurotrophic factor may protect the hair cell from aminoglycosides,the exact mechanism of HGF action to hair cells is still unknown.Materials and methods:We retrospectively identified 330 patients suffered from sensorineural hearing loss during the period from Jan 2010 to Mar 2014.10 subjects were obtained to the project,and was using the polymerase chain reaction(PCR)amplification reaction to investigate the PCR products of samples.Results:The 8 boys and 2 girls all suffered from profound hearing loss,and one was enlarged vestibular aqueduct,one was premature.We investigated 6 different types of mutations(c.299delAT.c.235delC、c.608T>C、c.109G>A、c.79G>A、c.341A>G),and 80%(8/10)patients carried at least one mutation.Three patients were carrying the homozygous pathogenic mutations.Conclusions:There was no between normal person and sensorineural hearing loss patients to diagnose an inguinal hernia,male vs female was 2.72:1(3.92%/1.44%),and the ratio of unilateral vs.bilateral was 9:1.SNHL patients with inguinal hernia were easier to GJB2 mutations than patients who only had SNHL.Chapter 4(section 4)Mutations of genes in 38 patients correlation with deafness:Analysis by genetic diagnosis kit for hereditary hearing lossIntroduction:The genetic diagnosis kit of hereditary hearing loss is different from the other traditional sequencing methods,such as low cost of money and time,high performance and is very accuracy.It’s able to perform mutations of four genes nine hot-spot.38 patients were joined the investigation.In the hope of surveying the etiology of the deafness,we use the genetic diagnosis kit to sequence their mutations of the four genes.Materials and methods:Thirty-eight patients were included in this study,they were outpatients,special pedigree patients,and profound non sensorineural hearing loss patients.Their gnomic DNA samples were used to perform mutation detection of 9 hot-spot mutations in four most common pathologic genes,including GJB2(c.35delG,c.176de116,c.235delC,c.299delAT),GJB3(c.538C>T,c.547G>A),SLC26A4(IVS7-2A>G,2168A>G)and mtDNA 12s rRNA(A1555G).Result:Of 38 patients,containing 21 males and 17 females,and 21(55.26%)patients were detected to have at least one pathogenic mutation.18.42%(7/38)patients were carried two pathogenic mutations.Among them,10(26.32%)have GJB2 gene c.235delC mutations,1 has c.176del16 mutation;9 have SLC26A4 gene c.IVS7-2A>G mutations;and 1 has mtDNA12Sr RNA gene c.1555A>G mutation.Conclusions:The genetic diagnosis kit for hereditary hearing loss preform well in sequence the mutation of genes,which make it suitable to clinic gene testing.