缝隙连接蛋白26基因相关性聋和大前庭水管综合征家庭的产前诊断和生育指导

Prenatal diagnosis for hereditary deaf families assisted by genetic testing

目的利用基因诊断方法为有再生育要求的耳聋家庭明确分子致病机制,并行产前诊断鉴别胎儿的基因型,为耳聋家庭提供准确的遗传指导与干预。方法共有8个耳聋家庭参加研究。8个家庭均有一个子女为重度-极重度感音神经性聋患儿,其中7个家庭(家庭1～7)父母均听力正常;1个家庭(家庭8)妻子为听力正常个体,丈夫为中度感音神经性聋个体。母亲均怀孕(6～28周)。所有受检患者均采集外周血并提取 DNA,进行缝隙连接蛋白26基因(gap junction beta-2,GJB2)、SLC26A4(或称 PDS)基因分析和线粒体 DNA(mtDNA)1555位点突变检测。明确受检者基因型后,根据母亲的妊娠时间,行适当的产前诊断取材并提取 DNA,测定胎儿的基因型。结果家庭1～4先证者均为 GJB2纯合或复合突变,父母均为携带者;家庭5～8先证者及家庭8父亲均为 SLC26A4复合突变,其余父母均为携带者。产前诊断显示:家庭1、5、8胎儿仅携带一个父系突变,家庭2、3、6胎儿未携带 GJB2或 SLC26A4突变,这6个家庭胎儿出生后随访听力均正常;家庭4、7胎儿与先证者基因型相同,父母选择终止妊娠。结论耳聋基因诊断结合产前诊断可以有效预防耳聋家庭再次生育聋儿。

Objective To provide prenatal diagnosis for deaf families, which the first child was confirmed to be hereditary deafness caused by gap junction beta-2 （GJB2） or SLC26A4 （PDS） mutation, to avoid another deaf birth in these families. Methods Eight deaf families joined in this study. Each family had one child with severe to profound hearing loss while parents had normal hearing except a deaf father from family 8 ; mothers had been pregnant for 6 - 28 weeks. Genetic testing of GJB2, SLC26A4 and mitochondrial DNA（mtDNA） A1555G mutation were firstly performed in probands and their parents whose DNA was extracted from peripheral blood, and then prenatal testing was carried out in the fetus whose DNA was extracted from different fetus materials depending on the time of gestation. Results The probands from family 1 -4 were found to carry homozygous or compound GJB2 mutations while their parents carried corresponding heterozygous GJB2 mutations. The probands from family 5 - 8 and the deaf father from family 8 were found to carry compound SLC26A4 mutations while their parents and the mother from family 8 carried a single SLC26A4 mutation. Prenatal testing showed that the fetuses from family 1, 5, 8 only carried the paternal mutation and the fetuses from family 2, 3, 6 didn＇t carry any GJB2 or SLC26A4 mutations. The new born babies from these six families all had normal hearing revealed by new born hearing screening. However, the fetuses from family 4,7 carried the same mutations with probands in each family. The parents from family 4,7 decide to terminate pregnancy. Conclusion Prenatal diagnosis assisted by genetic testing can provide efficient information about heating condition of their offsprings.