4个遗传性耳聋家庭的产前诊断及再生育指导

Prenatal diagnosis and second-birth guidance for 4 hereditary deafness families

目的采用基因诊断技术为遗传性耳聋家庭查明病因,对再生育的家庭提供产前诊断服务,明确胎儿的基因型,同时提供遗传咨询。方法选取2013年1月-2015年9月该院接诊的4个均有1个极重度感音神经性耳聋患儿的家庭,其中3个家庭的父母双方均为听力正常的个体,另一个家庭父母双方均为极重度感音神经性耳聋患者。抽取先证者及其父母的静脉血并提取DNA,用遗传性耳聋基因芯片对4个耳聋易感基因的9个突变进行分析,同时对耳聋基因芯片检测结果为杂合突变的病例进行GJB2和SLC26A4基因测序分析。明确受检者基因型后,对于有再生育需求的家庭,根据母亲妊娠时间,行适当的产前诊断取材并提取DNA,测定胎儿的基因型。对行产前诊断的新生儿进行随访。结果 4个家庭中,家庭1先证者为SLC26A4基因的复合杂合突变,父母双方均为杂合携带者;家庭2先证者为SLC26A4基因的复合杂合突变,父母双方均为SLC26A4基因的复合杂合突变;家庭3为GJB2基因的复合杂合突变,父母双方均为杂合携带者;家庭4先证者为SLC26A4基因的纯合突变,父母双方均为杂合携带者。产前诊断结果显示,家庭1和家庭3胎儿均携带母系突变,胎儿出生后随访听力正常;家庭4胎儿为突变携带者,未出生。结论遗传性耳聋的基因诊断结合产前诊断能有效防止聋儿的出生,是预防出生听力残疾的关键技术。

Objective To find out the causes of hereditary deafness using gene diagnosis,provide prenatal diagnosis service for second-birth families,confirm fetal genotypes and provide genetic counseling. Methods From January 2013 to September 2015,four families with one child of extremely severe sensorineural hearing loss in each were selected. In 3 families,the parents had normal hearing,while1 family had parents with extremely severe sensorineural hearing loss. The peripheral blood was collected from the deaf profound and their parents and DNA was extracted,followed by analysis of 9 mutation spots in 4 susceptible genes DNA microarray,heterozygotes GJB2 and SLC26A4 were analyzed by gene sequencing. For the families with second-birth needs,proper prenatal diagnosis sampling and DNA extraction were carried out to determine fetal genotypes during maternal pregnancy. These newborns were followed up. Results Among the four families,the profound from Family 1 was compound heterozygous SLC26A4 mutation with heterozygous carrier parents; the profound from Family 2 was compound heterozygous SLC26A4 mutation with parents of the same genotype; the profound from Family 3 was compound heterozygous GJB2 gene mutation,and the parents were heterozygous carriers; the profound from Family 4 was homozygous SLC26A4 mutation,and the parents were heterozygous carriers. Prenatal diagnosis showed that the fetuses from Family 1 and Family 3 carried maternal mutation with normal hearing; the fetus from Family 4 was not born with carrier of mutation. Conclusion Prenatal diagnosis assisted by genetic diagnosis can effectively prevent birth of deaf children,which is the key technology of hearing disability prevention.