中国西北地区线粒体DNA12SrRNAA1555G和GJB2基因突变

目的研究mtDNA 12SrRNA A1555G突变和GJB2突变在西北地区非综合征型感音神经性聋患者中的流行情况，探讨GJB2基因与mtDNA A1555G点突变的关系。方法收集本地区221例非综合征感音神经性聋患者的基因组DNA，多聚酶链反应扩增线粒体DNA和GJB2基因目的片断，Alw26Ⅰ限制性内切酶检测A1555G点突变，对酶切阳性病例和全部的GJB2基因的PCR产物进行DNA测序。结果21例患者检出mtDNA 12SrRNA A1555G突变；发现GJB2基因11种序列改变，有44例患者检出GJB2致病突变，235delC占携带致病突变患者的54．54％：在21例A1555G突变患者中，11例为GJB2基因多态改变，9例未检出GJB2基因序列改变，1例为109G→A（V371）突变。结论mDNA 12SrRNA A1555G在这一地区人群中有较高的发生频率．235delC是本地区GJB2基因突变的主要形式，GJB2基因突变不是mtDNA A1555G突变致聋的主要修饰因素。

Molecular analysis of mitochondrial DNA A1555G and connexin 26 gene(GJB2) in Chinese Northwest population with nonsyndromic sensorineural hearing loss

OBJECTIVE To investigate the incidence of the mitochondrial DNA 12SrRNA A1555G and connexin 26 gene (GJB2) in Chinese northwest population with nonsyndromic sensorineural hearing loss,and to explore the relationship between mitochondrial DNA A1555G and mutation of GJB2 gene. METHODS Blood samples were obtained from 221 patients with nonsyndromic sensorineural hearing loss in Northwest of China; Genomic DNA was extracted from the isolated leukocytes ; Screening the mitochondrial A1555G mutation by PCR-Alw26l digestion and sequence analysis, PCR and direct sequencing were used to analyze the coding region of GJB2 gene. RESULTS The homoplasmic A1555G mutation was found in 21 individuals of 221 patients,17 of these 21 patients had been treated with aminoglycosides. Eleven different variants of GJB2 were found in all patients ,the disease-causing mutations of GJB2 were 44 individuals in these patients(44/221), The mutation 235delC is found in 54.54 % of all disease-causing mutations ; Among 21 patients with the A1555G mutation, 11 cases were found polymorphic change in GJB2 gene ,only 1 case had V37I heterozygous mutations ,other 9 cases were not found any nucleotide changes of GJB2 gene. CONCLUSION The mtDNA 12SrRNA A1555G mutation has a high incidence in Chinese northwest population with non-syndromic sensorineural hearing loss.The 235delC mutation in the GJB2 gene is most frequent mutations responsible for non-syndromic hearing impairment in this region .It is unlikely that the GJB2 gene is a major modulatory factor for hearing loss due to the A1555G mutation in Chinese population.