摘要
目的探讨利用基因诊断方法先于颞骨CT诊断大前庭水管的可行性和优越性。方法两个家庭各有两个子女患神经性耳聋,家庭1后代为姐妹,家庭2后代为姐弟。所有患者和父母均采集外周血并提取DNA,以试剂盒方法检测PDS基因IVS7-2位点的A-G突变情况,并以序列分析方法分析外显子7+8和19的序列,两个家庭的耳聋患者均行颞骨CT检查。结果两个家系的共同特点为父母非近亲结婚,听力均正常,父母双方家族内无其他成员发生耳聋,但两个家庭均有两个子女患病,患者临床特征为有一定的残余听力,交流良好但发音略含混。试剂盒方法发现家庭1中两个患儿和其父母均见异常条带,Exon7+8序列分析结果显示家系1两个患儿均具有IVS7-2A-G纯合突变,其父母均携带IVS7-2A-G杂合突变,建议两个患儿行颞骨CT检查,报告均为前庭水管扩大。试剂盒方法发现家庭2中一个患儿和其母见异常条带,Exon7+8序列分析结果显示家系2具有异常条带患儿及其母具有IVS7-2A-G杂合突变,进一步的序列分析见此患儿及其父携带PDS2168A-G杂合突变,即此患儿具有PDS的复合杂合突变,随后的颞骨CT检查发现具有异常条带的患儿为前庭水管扩大,而病例4不具有PDS的复合突变,CT显示无前庭水管扩大。结论PDS基因诊断技术在具有PDSIVS7-2A-G热点突变的病例中可以成为颞骨CT的替代诊断工具首先诊断大前庭水管综合征,此项技术在常规耳聋病因学诊断、大规模耳聋患者的病因学筛查和远程医疗诊断方面有较好的应用前景。
Objective To evaluate the possibility and feasibility of PDS genetic testing as an alternative diagnostic tool for dilated vestibular aqueduct syndrome（DVAS）. Methods Two sisters from pedigree 1 and a sister and a brother from pedigree 2 all suffered from sensorinueral hearing loss. DNA were extracted from peripheral blood of all patients and their parents. PDS gene testing kit and direct sequencing were used to analyze the PDS genotype of all patients and their parents. All patients underwent high resolution temporal bone CT scan after genetic testing and hoth genetic testing and image data were compared. Results PDS Gene Testing kit showed abnormal pattern of electrophoresis bands in all four members of pedigree 1. Sequenee analysis showed that the sisters from pedigreel are homozygous for the splice site mutation （IVS 7-2 A-G） affecting the 3＇ splice site consensus sequence of intron 7. Their parents are heterozygous for the IVS 7-2 A-G mutation representing their carrier condition. The sister from pedigree 2 and her mother showed abnormal pattern of electrophoresis but the brother and their father didn＇t. The ease 3 is compound heterozygotes for IVS7-2 A-G mutation and 2168 A-G mutation meanwhile the ease 4 don＇t carry such compound mutations. The sister（case3） was confirmed to be enlarged vestibular aqueduct by temporal bone CT scan and the brother＇s temporal bone was normal. The genotype and image phenotype are consistent in pedigree 2. Conclusion Genetic testing for PDS gene is able to find the patients with DVAS prior to high resolution CT scan in patients with the PDS hot spot mutation IVS7-2 A-G. The method is suitable for early identification, molecular etiologic screening and remote diagnosis for DVAS.
出处
《中华耳科学杂志》
CSCD
2005年第4期241-244,共4页
Chinese Journal of Otology
基金
解放军总医院院长基金资助
教育部归国人员启动基金
