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目的利用基因诊断方法分析夫妻同为聋人的耳聋家庭的分子致病机制,为耳聋夫妇提供准确的遗传咨询和指导。方法 2005年7月至2006年6月期间共有4个耳聋家庭参加研究,4对夫妇均为重度到极重度聋患者。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(mtDNA)1555位点突变检测。结果家庭1丈夫未携带 GJB2、SLC26A4基因和 mtDNA A1555G 突变,妻子为 SLC26A4 IVS7-2A>G 和2168 A>G 复合突变,预测后代不论性别100%的可能为 SLC26A4基因突变携带者;家庭2丈夫与妻子均未携带 GJB2、SLC26A4基因和 mtDNA A1555G 突变,基本排除了后代因 mtDNA A1555G 突变、GJB2基因突变和 SLC26A4基因突变所致遗传性聋的可能性;家庭3丈夫为 GJB2 235delC 纯合突变及 SLC26A4 IVS7-2A>G 杂合突变;妻子确诊为大前庭水管综合征,但仅检测到 SLC26A4 IVS15+5 G>A 一个突变,由于 SLC26A4基因突变与大前庭水管综合征和耳蜗畸形有非常密切的关系,按理论推断还应有另一突变位点,预测后代不论性别均有50%可能为大前庭水管患者,50%可能为 SLC26A4基因突变携带者,同时肯定为GJB2基因突变携带者;家庭4丈夫为 mtDNA A1555G 突变携带者,妻子未携带 GJB2、SLC26A4基因和 mtDNA A1555G 突变,预测后代因线粒体基因 A1555G 突变、GJB2基因突变和 SLC26A4基因突变所致遗传性聋的可能性基本被排除。结论耳聋基因诊断可以为耳聋夫妇的遗传咨询和指导提供更加科学准确的理论依据。
OBJECTIVE: To analyze the molecular pathogenesis of deaf families with the same deafness by genetic diagnosis, and to provide accurate genetic counseling and guidance for deaf couple. Methods A total of 4 deaf families participated in the study from July 2005 to June 2006, and 4 of them were all severe to very severe deafness. All subjects were collected peripheral blood and DNA extraction, GJB2, SLC26A4 (PDS) gene analysis and mitochondrial DNA (mtDNA) 1555 site mutation detection. Results The family 1 husband did not carry the GJB2, SLC26A4 and mtDNA A1555G mutations, and his wife was a SLC26A4 IVS7-2A> G and 2168 A> G complex mutation. The offspring were 100% likely to be carriers of SLC26A4 mutations in their offspring. The family 2 husband and His wife did not carry the GJB2, SLC26A4 and mtDNA A1555G mutations, basically excluding the offspring due to mtDNA A1555G mutation, GJB2 gene mutation and SLC26A4 gene mutation caused by the possibility of genetic deafness; family 3 husband GJB2 235delC homozygous mutation and SLC26A4 IVS7 -2A> G heterozygous mutation; wife was diagnosed as a large vestibular aqueduct syndrome, but only detected SLC26A4 IVS15 +5 G> A a mutation, due to SLC26A4 gene mutation and vestibular aqueduct syndrome and cochlea deformity are closely related, According to the theory, there should be another mutation site. It is predicted that 50% of the offspring regardless of gender may be patients with large vestibular aqueduct, and 50% may be carriers of SLC26A4 gene mutation and are certainly carriers of GJB2 gene mutation. mtDNA A1555G mutation carrier, his wife did not carry GJB2, SLC26A4 gene and mtDNA A1555G mutation, the predicted offspring due to mitochondrial gene A1555G mutation, GJB2 The possibility of SLC26A4 gene mutation and gene mutation inherited deafness are basically excluded. Conclusion Deafness gene diagnosis can provide more scientific and accurate theoretical basis for genetic counseling and guidance of deaf couple.