基于基因诊断的耳聋遗传咨询、指导作用的初步观察

Genetic counseling and intervention for families with deaf-mute patients based on genetic testing:analysis of 5 families

目的利用基因诊断方法分析耳聋家庭的分子致病机制,并通过产前诊断进行胎儿耳聋基因型的鉴别,为不同发病原因的耳聋家庭提供准确的遗传咨询、指导和干预。方法共有5个耳聋家庭参加研究,其中3个家庭(家系1～3)均为父母听力正常,这3个家庭均有一个子女为中重度感音神经性聋患儿,受检时母亲均怀孕(6～18周)。1个家庭(家系4)夫妇均为聋哑人;1个家庭(家系5)丈夫为听力正常个体、妻子为重度耳聋个体。所有受检患者均采集外周血并提取 DNA,进行GJB2、SLC26A4(PDS)基因分析和线粒体 DNA 1555位点突变检测。结果家系1先证者携带 GJB2复合突变,父母为携带者,产前诊断显示胎儿仅携带一个父系突变,出生后随访听力正常;家系2先证者携带 SLC26A4(PDS)复合突变,父母为携带者,产前诊断显示胎儿仅携带一个父系突变,出生后随访听力正常;家系3先证者及其父母均未检出常见耳聋突变,第二胎出生后随访听力正常;家系4丈夫为 GJB2 235delC 纯合突变,妻子为线粒体 DNA A1555G突变阳性,建议其后代严格禁用氨基糖甙类抗生素;家系5妻子为 SLC26A4(PDS)复合突变,丈夫为 SLC26A4(PDS)杂合突变携带者,预测其后代患大前庭水管综合征(EVAS)的风险达到50%。结论耳聋基因诊断配合产前诊断在预防耳聋家庭再次生育聋儿上可以起明确的指导作用,并可引入正确的干预机制。

Objective To analyze the molecular genetic mechanisms of pathogenesis of deafness in the families with deaf-mute patients and analyze the strategies of genetic counseling and intervention for these families. Methods Peripheral blood samples were collected from the probands with deaf-muteness and their parents of five families and genetic tests were conducted to analyze the GJB2, SLC26A4 （PDS）, and mitochondrial DNA （mtDNA） A 1555G genes for the existence of mutation. Families 1-3 had one child with hearing loss each while the parents had normal hearing and the mothers had been pregnant for 6-18 weeks. Both parents of family 4 were deaf-mute, and the wife of family 5 was deaf-mute while her husband had normal hearing. Results The proband from family 1 was proven to carry compound GJB2 mutations while his parents carried a single GJB2 mutation; prenatal testing showed that the fetus only carried the paternal mutation. The proband from family 2 was proven to carry compound SLC26A4 （PDS） mutations while his parents carried a single SLC26A4 （PDS） mutation; prenatal testing showed that the fetus only carried the paternal mutation. The proband from family 3 and his parents didn＇t carry any GJB2, SLC26A4 and mtDNA A1555G mutation. Observation showed that the new born babies of these three families all had normal hearing revealed by new born hearing screening and ABR test. The husband from family 4 was homozygous GJB2 235delc while his wife was mtDNA A1555G positive. This couple was advised to strictly avoid the administration of aminoglycoside antibiotics to their future offspring. In family 5, the wife carried compound SLC26A4 （PDS） mutations while her husband carried a single SLC26A4 （PDS） mutation; and they were told about the 50% risk of their offspring＇ s suffering from enlarged vestibular aqueduct syndrome. Conclusion Genetic testing with prenatal testing and relevant intervention for the families with deaf-mute patients can be applied to prevent another deaf-mute member from being born.