摘要
目的对常染色体隐性遗传耳聋家系进行基因检测与产前分子诊断。方法收集先证者临床及家系资料,应用聚合酶链式反应(PCR)、限制性内切酶法检测,并用直接测序技术确认,对该家系成员的GJB2基因外显子进行序列分析。并运用STR位点分析方法排除产前诊断中母体基因组DNA的污染。结果家系1先证者GJB2基因分型为235delC/299-300delAT复合杂合突变,系重度感音神经性耳聋,父亲和母亲分别为299-300delAT和235delC杂合突变携带者,临床表型均正常。家系2先证者系235delC纯合突变,其父母均为235delC杂合突变携带者,具有正常听力表型。产前诊断结果显示,家系1和家系2胎儿GJB2基因分型分别为299-300delAT杂合突变和235delC杂合突变。结论 GJB2基因235delC纯合性突变和235delC/299-300delAT复合杂合突变均为耳聋致病突变,结合运用STR位点分析方法有助于在产前诊断中排除母体DNA对胎儿DNA的污染,产前诊断和早期干预能避免耳聋患儿的出生。
Objective To conduct genetic testing and attempt prenatal molecular diagnosis in families with hereditary recessive hearing loss. Methods Clinical and pedigree data from two probands were collected. The complete coding regions of the GJB2 gene from members of the families were amplified by polymerase chain reaction （PCR） and the PCR products were subjected to restriction fragment length polymorphism analysis and automatic DNA sequencing. In the process of prenatal mo- lecular diagnosis, maternal DNA contamination was excluded by the application of fluorescent STR profiling, which helped detecting the GJB2 gene profiling of the fetus. Results Compound heterozygous mutation of 235delc and 299-300delAT was detected in the proband of Pedigree 1 who showed profound sensorineural hearing loss. The proband＇ s parents showed normal phenotype, but were found to carry heterozygous GJB2 299-300delAT and 235delC mutations respectively. Homozygous 235delC mutation was detected in the proband of Pedigree 2, whose parents were found to carry the heterozygous 235delC mu- tation with normal hearing. Prenatal diagnostic tesing showed that fetuses from Pedigrees 1 and 2 were carriers of the GJB2 gene 299-300delAT heterozygous mutation and GJB2 gene 235delC heterozygous mutation. Conclusion Both homozygous 235delC mutation and the compound heterozygous mutation of 235delC and 299-300del are pathogenic mutations. Fluorescent STR profiling helps exclude maternal DNA contamination in prenatal molecular diagnosis. Prenatal molecular diagnosis and early intervention can prevent the birth of deaf children.
出处
《中华耳科学杂志》
CSCD
北大核心
2012年第3期360-363,共4页
Chinese Journal of Otology
基金
2009年广东省科技计划项目
项目编号:2009B030801233
