Study On Prevention And Intervention For Hereditary Hearing Loss Based On Genetic Testing

Genetic testing exerted a great influence and brought evolutionary progress on diagnosis and prevention for deafness. Based on the results of the national epidemiological study for deafness that a large proportion of both syndromic and nonsyndromic forms of deafness are caused by a small number of genes, genetic testing has been implemented clinically and the followed is coming up with the new idea of prevention for deafness. This study focused on the thoroughly prevention and intervention for hereditary hearing loss, including genetic testing and counseling for deaf youth before marriage; genetic testing and prediction of offspring's hearing status for deaf couples; genetic testing and prenatal diagnosis for couples who have a deaf child; carrier screening of common deaf genes in pregnant women, in order to provide evidence and theory for the national strategy of prevention for deafness, promote the application of genetic testing in China and eventually reduce the birth rate of deaf children.Part I:The prevention and intervention for hereditary in population with high deaf recurrence riskChapter I Genetic Counseling and Instruction for Deaf Youth Directed by Genetic TestingIn our survey,40% deaf youth are willing to have a deaf spouse and that means the deaf youth is the potential population with "deaf-deaf" marriage mode.This marriage mode will increase the possibility of marriage between the deaf youth caused by same deaf genes,and the deaf couples caused by same deaf genes will increase the number of newborn babies if without the intervention. To decrease the risk of having the deaf offspring,the deaf youth caused by GJB2 or SLC26A4 mutations need to avoid the deaf spouses or carriers caused by same deaf genes, and this can be realized by means of genetic testing before marriage.In this study,293 deaf youth,age 16-27,received the genetic testing. The carrier rate of GJB2, SLC26A4 and mtDNA A1555G mutation were 20.1%,12.3% and 7.5% retrospectively, and 54.5% mtDNAA1555G mutation carriers were female. Then the genetic information and instruction before marriage were offered to them based on results.ChapterⅡGenetic Counseling and Instruction for Deaf Couples Directed by Genetic TestingThe marriage mode of 'deaf—deaf' is very common in deaf population. Most of deaf couples are eager to receive effective genetic counseling to avoid having a deaf offspring. By means of genetic testing, we analyzed the molecular pathogenesis of 100 deaf couples (200 individuals altogether).118 individuals (58%) were confirmed to be hereditary deafness caused by GJB2, SLC26A4 or mtDNA mutation. There were high deaf recurrence risk in 34 deaf couples.22 of them confronted recurrence risk as high as 100%, as each couple were caused by same deaf genes(GJB2 or SLC26A4).8 of them were with 50% recurrence risk. The offspring in 3 couples with deaf wives caused by mtDNAA1555G mutation would be the same mutation carriers and the the instruction for them was to strictly avoid the administration of aminoglycoside antibiotics. The following visit showed that 2 deaf offspring were avoided and 18 deaf couples gave the birth to normal hearing babies. ChapterⅢ. Prenatal Diagnosis for hereditary deaf families assisted by genetic testingTo be assisted by genetic testing, prenatal diagnosis was carried out in 213 hereditary deaf families.The recurrent risk was 25% in 209 families, including 204 families with one deaf child and 5 families without children, which all couples were GJB2 or SLC26A4 mutation carriers and deaf children were caused by homozygous or compound GJB2/SLC26A4 mutations; The recurrent risk was 50% in 3 families, which one family was of the father and his child with compound SLC26A4 mutations and the mother with heterozygous SLC26A4 mutation, one family was of the wife with POU3F4 c.647G>A heterozygous mutation and the rest one family was of the husband with compound SLC26A4 mutations and the wife with mtDNA A1555G mutation and heterozygous SLC26A4 mutation simultaneously; The recurrent risk was 100% in one family of the deaf couple both caused by GJB2 mutations, and the deaf wife got pregnant by means of artificial insemination with the sperm from the local Human Sperm Bank.226 times of prenatal testing were applied in all 213 families.46 times of prenatal testing showed that the fetuses carried parental mutations simultaneously or the same mutations with probands, and the parents decided to terminate pregnancy; while 180 times of prenatal testing showed that the fetuses carried only one parental mutation or did not carry any mutation from parents, and the following visit showed that 141 families had given birth to babies who were all revealed to have normal hearing by new born hearing screening. Prenatal diagnosis assisted by genetic testing can provide scientific information about offspring's hearing condition, and the normative workflow and precise strategy highly guarantee the safe and favorable implementation of prenatal diagnosis. PartⅡ:The Genetic Screening of Common Deaf genes in Pregnant Women and Intervention for deaf birth defectSince the carrier rate of common deaf genes in China is as high as 6%, only depending on the prevention and intervention of hereditary deafness in deaf population is not enough to stop the transmitting of deafness in whole population.Genetic screening for young couples can find out the couples who are the same deaf genes' carriers and then avoid to have deaf offspring.In addition, mtDNA mutation carriers who are sensitive to aminoglycoside antibiotics and individuals with late on-set hereditary deafness can be found in time by means of genetic screening of deaf genes in pregnant women and newborn babies. Early intervention and rehabilitation can prevent them from being deaf. In this study, we carried out genetic screening of common deaf genes in 3000 pregnant women.146 women (4.9%) were confirm to carry common deaf gene's mutations.91 women(3.03%) were GJB2 carriers,49(1.63%) were SLC26A4 carriers and 6(0.2%) were mtDNA A1555G carriers. The further analysis showed that 12 couples were the same deaf genes(GJB2/S1C26A4) carriers, which means their offsprings would confront 25% deaf risk. The following genetic instruction and prenatal diagnosis assisted them to avoid deaf offsprings. We also finished the following visit in 3000 women and there was no deaf offspring reported. This is the first time to accomplish the primary prevention for deafness in normal hearing population.