Mitochondrial DNA mutations in patients with postlingual, nonsyndromic hearing impairment
Mitochondrial DNA mutations in patients with postlingual, nonsyndromic hearing impairment
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DOI：
10.1038/sj.ejhg.5201250
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发表时间：
2005-01-01
影响因子：
5.2
通讯作者：
Mueller, RF
中科院分区：
文献类型：
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作者：
Jacobs, HT;Hutchin, TP;Mueller, RF
线粒体突变以前曾在母系遗传的非综合征性听力障碍家族中报道过。为了确定线粒体突变对语后但早发性、非综合征性听力损伤的作用，我们筛选了来自两个不同人群（意大利南部和英国）的患者，以寻找先前报道的与听力障碍相关的线粒体DNA突变。引物延伸（SNP分析）用于筛选特定突变，揭示异质性及其程度的情况。最常涉及的tRNA基因Leu（UUR）和Ser（UCN）也在所有意大利患者中进行了测序。对这些英国患者的所有tRNA基因进行测序，显示出最明显的母系遗传可能性。在这两个人群中，约5%的患者中发现了致病性mtDNA突变，占明显家族性病例的近10%。已知的发病年龄通常在成年期之前，听力损失通常是进行性的。单倍群分析显示，与人群对照组相比，患者中可能存在过量的单倍群簇HV，但具有边缘统计学意义。相比之下，我们没有发现任何先前报道的mtDNA突变，也没有显着偏离典型的对照人群的单倍型群簇频率，在英国或芬兰的晚发性成人听力损失（年龄相关性听力损伤）患者。
Mitochondrial mutations have previously been reported anecdotally in families with maternally inherited, nonsyndromic hearing impairment. To ascertain the contribution of mitochondrial mutations to postlingual but early-onset, nonsyndromic hearing impairment, we screened patients collected from within two different populations (southern Italy and UK) for previously reported mtDNA mutations associated with hearing disorders. Primer extension (SNP analysis) was used to screen for specific mutations, revealing cases of heteroplasmy and its extent. The most frequently implicated tRNA genes, Leu(UUR) and Ser(UCN), were also sequenced in all Italian patients. All tRNA genes were sequenced in those UK patients showing the clearest likelihood of maternal inheritance. Causative mtDNA mutations were found in approximately 5% of patients in both populations, representing almost 10% of cases that were clearly familial. Age of onset, where known, was generally before adulthood, and hearing loss was typically progressive. Haplogroup analysis revealed a possible excess of haplogroup cluster HV in the patients, compared with population controls, but of borderline statistical significance. In contrast, we did not find any of the previously reported mtDNA mutations, nor a significant deviation from haplogroup cluster frequencies typical of the control population, in patients with late adult-onset hearing loss (age-related hearing impairment) from the UK or Finland.