208例非综合征性耳聋患者的基因诊断与产前诊断

Genetic analysis and prenatal diagnosis for patients with non-syndromic hearing impairment

目的明确非综合征性耳聋患者的分子学病因,并对高危胎儿进行产前诊断。方法以208例非综合征性耳聋患者为研究对象,应用耳聋基因芯片,针对GJB2、SLC26A4、GJB3以及线粒体12 S rRNA基因的9个突变位点进行检测,对检测出GJB2或SLC26A4基因单杂合突变者41例进行相应基因扩增并测序。对2例高危胎儿通过GJB2或SLC26A4基因测序进行产前诊断。结果 208例患者中,86例通过基因芯片检出突变位点,检出率41.35%(86/208),检出2个突变位点者40例,检出1个突变位点者46例。最常见为GJB2基因235del C突变,共46例患者检出,检出率22.12%(46/208)。对其中41例GJB2或SLC26A4基因单杂合突变患者进行测序,有12例检出另一突变,使检出2个突变的患者增加至52例,明确诊断率达到25.00%(52/208)。对2个高危胎儿进行产前诊断,家系1胎儿为299-300del AT和235del C复合杂合突变患儿。家系2胎儿为IVS7-2A>G携带者。结论基因芯片结合Sanger测序是对非综合征性耳聋患者进行基因诊断的有效方法,对高危胎儿进行产前诊断是优生优育的重要手段。

Objective To explore the genetic pathogen of patients with non-syndromic hearing impairment and to provide prenatal diagnosis for the families of hereditary deafness. Methods Mutation screening of GJB2, SLC26A4, GJB3 and mitochondrial 12 S rRNA genes was performed in 208 patients with non-syndromic hearing impairment by gene chip. Then direct sequencing was used in 41 patients who were found one mutation of GJB2 or SLC26A4 gene. And prenatal diagnosis was carried out in two families by direct sequencing. Results Eighty-six patients （41.35%） were found at least one mutation by gene chip. Among them, 40 patients were found to carry two mutations and 46 patients were found to carry one mutation. The most frequent mutation was 235delC, which was found in 46 patients. And 12 cases were found the second mutation through direct sequencing. A total of 52 （25.00%） patients were detected two mutations. Prenatal diagnosis showed that one fetus carried compound mutations of 299-300delAT and 235delC, and another one carried heterozygous mutation of IVS7-2A〉G. Conclusion Patients with non-syndromic hearing impairment can be accurately diagnosed by gene chip and Sanger sequencing. The prenatal diagnosis is primary means for high-risk fetuses.