家族性大前庭水管患者的PDS基因型分析

目的：分析2个大前庭水管家系中患者的临床表现及基因型。方法：应用PDS（SLC26A4）基因检测方法进行2个家系成员的基因型分析。所有患者和父母均采集外周血，以试剂盒方法提取DNA。先行Exon7＋8序列分析，未见突变后再扩增其余17个片段，以覆盖PDS基因全部cDNA序列及每个外显子前后的剪切区序列，以变性高效液相色谱仪分析每个扩增子，如待测标本与对照组标本的混合物的过柱波形与对照组相比有前移、后移或有明显的波形畸变，特别是出现2～4个波峰，则判定为待测标本的扩增片段内可能存在序列变异，将此待测标本的扩增子进行全自动序列分析。结果：2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2个家系均有2个子女患病，患者临床特征为听力进行性下降，交流良好，但发声略含糊。家系1孪生姐妹在2年内3次纯音测听呈现听阈进行性增高；Exon7＋8序列分析结果显示孪生姐妹均具有IVS7—2A—G纯合突变，其父母均携带IVS7—2A—G杂合突变。家系2先证者发现DHPLC异常波形2个，分别分布在外显子2和外显子10，序列分析发现先证者的外显子10存在T410M和1199ins T复合突变，其兄具有同样的复合突变。结论：家族性大前庭水管综合征是典型的遗传性疾病，单个家族内患病个体具有相似的临床表现和相同的变异基因型。

Genotypic analysis of familial dilated vestibular aqueduct syndrome

Objective:To analyze clinical manifestation of patients from two families with dilated vestibular aqueduct syndrome(DVAS). Their genotypic patterns were discriminated with the genetic testing methods for PDS gene.Method:The twin sisters from pedigree1 and the brother and sister from pedigree 2 all suffered from sensorinueral hearing loss. All patients from these two families were confirmed to have enlarged vestibular aqueduct by temporal bone CT scan. Exon 7 8 and their flanking area sequences were analyzed by direct sequencing. All other exons and their flanking sequences were screened by DHPLC. The amplicons of exons which showed abnormal DHPLC wave pattern were further sequenced.Result:The parents of two families are non-consanguineous, hearing normal couples with no other family members with hearing loss. Both families have two offspring with DVAS. The clinical features of all patients were progressive hearing loss, good communication ability but with thickness pronunciation. Both twin sisters from pedigree1 are homozygous for the splice site mutation (IVS 7-2 A-G) affecting the 3' splice site consensus sequence of intron 7. The brother and sister of pedigree 2 are compound heterozygotes for 1199 ins T mutation and a missense mutation (1229 C-T).Conclusion:Familial DVLS is typical hereditary disease. The patients with DVLS have similar clinical manifestation and the same genotypic changes in PDS.