一个遗传性耳聋大家系的基因突变检测

目的 :探讨中国人遗传性耳聋基因的突变热点和明确我们最近收集到的一个遗传性耳聋家系是否为已克隆的耳聋基因的突变所致。方法 :该家系 5代共 4 7人 ,其中耳聋患者 1 8人 ,从家系图分析 ,符合常染色体显性遗传 ;所有患者均为语后聋 ,从 1 6 3 0岁起病 ,为双耳对称性、进行性、高频听力下降为主的感觉神经性聋 ,不伴其它器官系统的异常 ;采用PCR 直接测序法在该家系中进行HDIA1、GJB3、GJB2、DFNA5、а tectorin(可导致DFNA8和DFNA1 2两型遗传性耳聋 )、MYO7A、POU4F3等 7个常染色体显性耳聋基因的突变检测。结果 :发现CX2 6基因有 2种核苷酸改变即A3 4 1G和GC2 5 7 2 5 8CG ;POU4F3基因有 1种核苷酸改变即T90C。分析后发现 ,上述核苷酸改变均不是该家系耳聋的致病性突变。其余 5个基因未发现突变。结论 :该常染色体显性耳聋家系由目前已克隆基因突变所致的可能性较小 ,笔者目前正在进行的全基因组扫描和连锁分析极有可能定位一个新的耳聋基因位点

An analysis of a large hereditary postlingually deaf families and detecting mutation of the deafness genes

OBJECTIVE: To make a further exploration of the mutation frequence of Chinese genetic deafness and make clear if the genetic deafness genealogy that we collected recently was resulted from the mutation of the deafness genes which had been cloned. METHOD: We made regular otologic examination, hearing test and physical examination among the members of this genealogy, and also inspected the mutation of seven autosomal domiant deafness genes, HDIAI,GJB2, GJB3, DFNA5, a-tectorin(resulting in two types of genetic deafness, DFNA8 and DFNA12), MYO7A,POU4F3, with PCR-Sequencing method in this genealogy. RESULT: 1.The analysis of hereditary mode: There were forty-seven persons collected in five generations of this genealogy, and eighteen persons of them were deafness. It accorded with autosomal dominant inheritance from the pedigree. 2. The clinic feature: All patients with deafness were postlingual deafness. Their hearing decreased onset between sixteen to thirty years old, and the deafness was binaural symmetrical, progressive sensorineural and without other systems abnormity. 3. Analysis of mutation detection: We found two nucleotides changes in CX26 genes, A341G and GC257-258CG, and one changed nucleotide in POU4F3 gene,T90C. But we didn't think the changed nucleotides caused deafness after we analysed them. No mutation was found in other five genes. CONCLUSION: The possibility that the deafness of this genealogy was resulted from the cloned gene is relatively small. Now, We are scanning the whole gene groups and making linkage analysis on this pedigree, it is most probably to orientate a new deafness gene position.