一个同时携带线粒体DNA A1555G突变和GJB2 235delC单杂合突变家系的基因型与听力表型

GJB2 235delC single allelic mutation modulates the phenotype associated with the mitochondrial AI555G mutation

目的调查一个同时携带线粒体DNA A1555G突变和GJB2 235delC突变的非综合征型耳聋家系，分析其基因型和听力表型的关系。方法对家系成员进行临床听力测试，收集家系中8名成员的外周静脉血样本，从自细胞中提取DNA，聚合酶链反应扩增GJB2基因和线粒体DNA（mitochondric DNA，mtDNA）目的片段，对扩增片段直接测序进行GJB2基因、mtDNA 12S rRNA及tRNA^Ser（UCN）基因突变分析。结果此家系先证者存在mtDNA A1555G突变和GJB2 235delC杂合突变，听力表型为极重度感音神经性耳聋。其他母系成员携带mtDNA A1555G突变，未发现tRNA^Ser（UCT）基因突变。家系中其他母系成员听力表型为双侧对称高频下降或听力正常。结论GJB2 235delC单杂合突变可能参与了mtDNA A1555G的听力损害。

Objective To investigate a non-syndromic deafness family in which potential interaction between the GJB2 gene and a mitochondrial gene appeared to be the cause of hearing impairment. Methods Audiological examination was performed by pure-tone audiometry （PTA）. Blood samples from 8 members of the pedigree were obtained. DNA was extracted from the leukocytes. The coding region of the GJB2 gene and mitochondrial DNA target fragments were amplified by polymerase chain reaction （PCR）. The PCR products were analyzed by sequencing. Results Direct sequencing showed that the proband had both a heterozygous mutation of 235delC in the GJB2 gene and a mitochondrial 1555 A to G mutation. The proband had profound hearing loss. The maternal relatives had sensorineural hearing loss in the higher frequencies or no hearing loss. Conclusion The GJB2 mutations may bean aggravating factor in the phenotypic expression of the non syndromic hearing loss associated with the A1555G mitochondrial mutation.