tRNASer(UCN)7472delC可能是耳聋与癫痫相关的线粒体基因新突变

线粒体DNA突变与许多人类疾病的发病机制相关。文章报道1例典型的患有耳聋与癫痫症状的具有母系遗传特征的中国家系。该家系共3代人, 其中14名母系成员中有3名耳聋患者, 3名癫痫患者, 而其他成员则无临床症状。线粒体全基因组序列分析表明, tRNA^Ser(UCN)基因7472delC新突变和33个多态位点属于东亚单体型B4b1a2。7472delC突变位于tRNA^Ser(UCN)高度保守的T-arm上。而在该区域的相同位点7472insC突变已在多个无遗传相关的家系中被发现与耳聋和癫痫相关。7472insC突变使tRNA代谢和线粒体功能产生缺陷。这样与7472insC突变相近的7472delC突变可能也会以相似机制引起线粒体功能障碍。同时, 在该家系中未发现GJB2基因及其他线粒体基因突变。因此, ^tRNASer(UCN) 7472delC可能是耳聋与癫痫相关的线粒体基因新突变。

Hearing loss and epilepsy may be associated with the novel mito-chondrial tRNASer(UCN) 7472delC mutation in a Chinese family

Mutations in mitochondrial DNA have been associated with a wide spectrum of clinical abnormalities. We reported here the clinical and genetic evaluations as well as mutational analysis of mitochondrial DNA(mtDNA) in a three-generation Chinese Han family with maternally transmitted hearing loss and epilepsy. Of 14 matrilineal relatives, three suffered from hearing loss, three had epilepsy, and other did not have significant clinical abnormalities. Sequence analysis of mitochondrial genome in this family identified the novel 7472delC in tRNA^Ser(UCN) and 33 variants belonging to Asian haplogroup B4b1a2. The 7472delC locates at the highly conserved residue of T-arm of this tRNA. In fact, the 7472insC at the same position of this tRNA has been associated with hearing loss and epilepsy in several genetically unrelated families. The 7472insC has been shown to lead to a failure in tRNA metabolism and mitochondrial dysfunction. Thus, 7472delC mutation, similar to 7472insC mutation, may result in the mitochondrial dysfunctions responsible for the hearing loss and epilepsy. Furthermore, none of mutation in deafness-associated GJB2 gene was detected in this Chinese family. Therefore, the 7472delC is likely a new mitochondrial mutation with hearing loss and epilepsy.