论文标题:基于基因诊断的耳聋遗传咨询与产前诊断
Genetic Counseling and Prenatal Diagnosis for Hearing Loss Based on Genetic Testing
论文作者
论文导师 戴朴,论文学位 硕士,论文专业 耳鼻咽喉
论文单位 中国人民解放军军医进修学院,点击次数 98,论文页数 124页File Size12242K
论文网 http://www.lw23.com/lunwen_176180112/
hereditary hearing loss; GJB2 gene; SLC26A4 gene; Mitochondrial DNA (mtDNA); genetic testing; genetic counseling; prenatal diagnosis
随着人类基因组计划的顺利完成，关于遗传性耳聋方面的研究取得了卓越的成就。人们发现中国绝大部分遗传性耳聋患者是由GJB2、SLC26A4和线粒体基因突变导致，利用基因诊断技术对这三个基因检测，不仅可为绝大部分遗传性耳聋患者明确病因，而且为耳聋遗传咨询提供了理论依据及科学手段，使其更客观准确，同时使得对于遗传性耳聋家庭的产前诊断成为可能。本研究利用基因诊断技术对耳聋遗传咨询及产前诊断进行了较为系统的实践，摸索建立制定相关流程与策略，同时对耳聋家庭的再发风险、聋人与聋儿家长对基因检测的态度进行了初步调查与统计。本研究主要包括以下两个部分： 第一部分基于基因诊断的耳聋遗传咨询 基因诊断技术的诞生大大促进了耳聋遗传咨询工作的发展。利用耳聋基因诊断技术，本研究对217例青年聋人、4对聋哑夫妇及30个有再生育要求的耳聋家庭进行了系统的耳聋遗传咨询实践，为上述不同类型的遗传咨询对象提供了相应的遗传信息与指导，总结出耳聋遗传咨询的流程与策略。此外，本研究还对605个耳聋家庭的再发风险进行了初步调查与统计，发现耳聋家庭的再发风险较高；同时调查了124名青年聋人及107名聋儿家长对耳聋基因检测的态度，发现青年聋人与聋儿家长普遍持积极态度，两项调查结果对耳聋遗传咨询有很好的帮助与指导作用。 第二部分遗传性耳聋家庭的产前诊断 利用耳聋基因诊断技术，本研究为16个有再生育要求的耳聋家庭明确了分子致病机制，并行产前诊断鉴别胎儿的基因型，为这些家庭提供了准确的遗传指导与干预。这16个家庭中，12个家庭产前诊断显示胎儿不会复制先证者的听力结构，其中6个家庭的胎儿已出生，随访听力正常，另6个家庭的母亲目前在待产中；余下4个家庭产前诊断显示胎儿与先证者的基因型相同，家长自己选择终止妊娠。通过本研究说明耳聋基因诊断配合产前诊断可以有效预防耳聋家庭再次生育聋儿。
With the project of human genome being completed, there has been remarkable progress being made on hereditary hearing loss. Since the majority of Chinese hereditary deaf people have been confirmed to be caused by GJB2 gene、 SLC26A4gene and mtDNA mutations, genetic testing of these three genes can assist us with making clear about cause of deafness and providing theoretical evidences for genetic counseling which make genetic information and instruction more scientific and accurate. Furthermore, it makes prenatal diagnosis possible for deaf families. By means of genetic testing, we systematically carried out the clinical practices of genetic counseling and prenatal diagnosis for Chinese deaf people and families; meanwhile, we took the preliminary survey on recurrence risk of deaf families and the attitude of deaf youth and parents from deaf families towards genetic testing.Part one: Genetic counseling for deafness based on genetic testing.Genetic testing has promoted the development of genetic counseling undoubtly. By means of genetic testing, we carried out the clinical practices of genetic counseling for 217 deaf youths, 4 deaf couples and 30 deaf families that the parents hoped to have a normal hearing baby. We provided more accurate genetic information and instruction for these counseling subjects based on results of genetic testing and then set up the procedure and strategy of genetic counseling for deafness. Besides, we took a survey on recurrence risk of 605 deaf families and reached to preliminary statistical results which showed that the recurrencerisk of deaf families is very high; meanwhile we also investigated 124 deaf young adults and 107 parents from deaf families about the attitude towards genetic testing and the results demonstrated most of them have the positive attitude. Results from the two surveys will be helpful for genetic counseling.Part two: Prenatal diagnosis for hereditary deaf families assisted by genetic testingBy means of genetic testing, we analyzed the molecular pathogenesis of 16 deaf families expecting to have a normal hearing baby whose first children are all deaf, confirmed that probands were caused by GJB2 or SLC26A4 mutations and then provided prenatal diagnosis for these families. Among the 16 deaf families, 12 fetuses were confirmed to only carry a single or no GJB2 or SLC26A4 mutations. 6 of the 12 fetuses have been given the birth and all had normal hearing revealed by new born hearing screening. The other 6 fetuses" mothers are still in pregnant. The rest 4 fetuses carried the same mutations with probands and their parents decided to terminate pregnancy. Prenatal diagnosis assisted by genetic testing can provide efficient information about hearing condition of their offsprings and avoid another deaf birth.
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