【摘要】 目的探讨修饰因子对线粒体A1555G突变相关非综合征型聋的影响。方法对携带线粒体A1555G突变的27个家系69例非综合征型聋患者进行听力学和分子遗传学评估。结果 27个家系平均听力损失患者发病年龄11.96岁,排除氨基糖甙类抗生素接触史者,年龄上升为15.21岁;家系3代内平均听力损失外显率40.96%,排除有氨基糖甙类抗生素接触史者,外显率降至33.45%。27个家系分属8种不同单倍型,并携带tRNAIleA4317G、tRNAGlnC4387T、tRNASer(UCN)T7492C和tRNAThrC15910T四个继发突变。检测到2例GJB2 235 delC纯和突变,1例GJB2 235 delC杂合突变。此外,患者主要表现为轻、中度高频听力损失类型,多为语后聋。结论氨基糖甙类抗生素、线粒体单倍型及继发突变、GJB2和发病年龄等因素可能参与了携带线粒体A1555G突变者的表型修饰。更多还原

【Abstract】 OBJECTIVE To investigate the effect of modifier factors on mitochondrial A1555G mutation-related nonsyndromic impairment. METHODS An audiological and molecular genetic evaluation of 69 patients with nonsyndromic impairment in 27 pedigrees with mitochondrial A1555G mutation was performed. RESULTS The mean age of onset of deafness in 27 families was 11.96 years old, and the mean age of patients without a history of exposure to aminoglycoside antibiotics increased to 15.21 years old. The average penetrance rate of deafness within 3 generations of the families was 40.96%. And excluding patients with aminoglycoside antibiotic exposure, the penetrance rate decreased to 33.45%. The 27 pedigrees belonged to 8 different haplotypes and carried 4 known secondary mutations of tRNA Ile A4317G, tRNAGlnC4387T, tRNASer(UCN) T7492C and tRNA Thr C15910T, which may enhance the penetrace of hearing loss in these families. In addition, two patients with pure mutation and one with heterozygous mutation of GJB2 235 delC were detected. Moreover, patients were mainly presented with mild and moderate high frequency hearing loss, and mostly with post-verbal deafness. CONCLUSIONThese observations suggested that aminoglycoside antibiotics, mitochondrial haplotypes, secondary mutations, mutation of GJB2 and the age of onset may modulate the variable penetrance and expressivity of deafness among these pedigrees.更多还原