摘要
目的对两个常染色体隐性遗传耳聋家系进行基因突变分析及产前诊断。方法收集家系成员外周血样本及临床资料,运用PCR产物直接测序技术对家系所有成员进行GJB2、GJB3、SLC26A4、线粒体12S r RNA 4个耳聋相关基因检测,明确耳聋致病基因;结合STR位点分析方法排除产前诊断中胎儿DNA受母体基因组的污染。结果家系1先证者系GJB2基因109G>A/235del C复合杂合突变;家系2先证者为SLC26A4 IVS7-2A>G/946G>T复合杂合突变;产前诊断结果显示家系1和家系2胎儿分别系109G>A杂合突变携带者及SLC26A4基因IVS7-2A>G杂合突变携带者。结论 GJB2基因109G>A与235del C所形成的复合杂合突变可导致重度感音神经性耳聋,DNA片段测序技术有助于寻找耳聋致病基因非热点突变,产前诊断和早期干预能避免耳聋患儿的出生。
Objective： To conduct genetic analysis and attempt prenatal molecular diagnosis in two Chinese families with autosomal recessive inheritance heating loss. Methods： Blood samples and clinical data of all members from two families were collected. The four deafness related genes, GJB2, GJB3, SLC26A4 and 12SrRNA gene, from members of the families were amplified by polymerase chain reaction （PCR） and the PCR products were subjected to automatic DNA sequencing. Maternal DNA contamination were excluded by application of STR analyzing in the process of prenatal molecular diagnosis. Results： Compound heterozygous mutation of 109G〉A and 235delC in GJB2 gene was detected in the proband of Pedigree1 who presented sever sensorineural hearing loss, whereas the proband of Pedigree2 carried alien heterozygous mutation, IVS7-2A〉G and 946G〉 T, of SLC26A4 gene. Prenatal molecular diagnostic testing reviewed the heterozygous mutation of 109G〉A in GJB2 and IVST-2A 〉G in SLC26A4 gene in two fetuses from pedigree 1 and 2, respectively. Conclusion： Compound heterozygous mutation of 109G 〉A and 235delC in GJB2 could causes sever sensorineural hearing loss. DNA Sequencing can contributes to find the rare underlying pathogenic mutations in deafness patients. Prenatal molecular diagnosis and early intervention can prevent the birth of children with hearing loss.
出处
《中国优生与遗传杂志》
2016年第2期19-21,F0002,共4页
Chinese Journal of Birth Health & Heredity
基金
温州市公益性科技计划项目(项目编号:Y20140477)
