Molecular and clinical characterisation of three Spanish families with maternally inherited non-syndromic hearing loss caused by the 1494C→T mutation in the mitochondrial 12S rRNA gene
Molecular and clinical characterisation of three Spanish families with maternally inherited non-syndromic hearing loss caused by the 1494C→T mutation in the mitochondrial 12S rRNA gene
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DOI：
10.1136/jmg.2006.042440
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发表时间：
2006-11-01
影响因子：
4
通讯作者：
del Castillo, I.
中科院分区：
文献类型：
--
作者：
Rodriguez-Ballesteros, M.;Olarte, M.;del Castillo, I.
线粒体基因组 12S rRNA 基因的突变导致母系遗传的非综合征性听力损失 (NSHL)，并增加对氨基糖苷类抗生素耳毒性的易感性。在这些突变中，1555A -> G 是迄今为止测试的所有人群中最常见的。最近，在两个母系遗传的 NSHL 中国大家系中报道了 1494C -> T 突变。在这项研究中，对一个母系遗传的 NSHL 西班牙家族的 12S rRNA 基因进行测序，结果显示存在 1494C -> T 突变。作者对 1339 名无关的西班牙 NSHL 患者进行了额外筛查，发现了另外两个携带该突变的家族。从 17 名确诊的 1494C -> T 携带者中获得的听力学数据显示，听力损失是感音神经性、双侧和对称性的，发病年龄和严重程度存在显着差异。三名携带者没有症状。三名受影响的携带者有氨基糖苷类抗生素治疗史。对这三个家族各一名受影响者的线粒体基因组进行了完整测序，并确定他们属于不同的线粒体单倍群（H、U5b、U6a）。研究结果进一步支持了1494C→T对听力的致病作用，并表明这种突变可以在不同的白种人线粒体DNA背景中发现。
Mutations in the 12S rRNA gene of the mitochondrial genome are responsible for maternally inherited non-syndromic hearing loss ( NSHL), and for increased susceptibility to the ototoxicity of aminoglycoside antibiotics. Among these mutations, 1555A -> G is the most prevalent in all populations tested so far. Recently, the 1494C -> T mutation was reported in two large Chinese pedigrees with maternally inherited NSHL. In this study, sequencing of the 12S rRNA gene in a Spanish family with maternally inherited NSHL showed the presence of the 1494C -> T mutation. An additional screening of 1339 unrelated Spanish patients with NSHL allowed the authors to find two other families with the mutation. Audiological data were obtained from 17 confirmed 1494C -> T carriers, which showed that the hearing loss was sensorineural, bilateral and symmetrical, with a remarkable variability in age of onset and severity. Three carriers were asymptomatic. Three affected carriers had a history of treatment with aminoglycoside antibiotics. The mitochondrial genome of one affected person from each of these three families was entirely sequenced, and it was established that they belong to different mitochondrial haplogroups ( H, U5b, U6a). The study results further support the pathogenic role of 1494C -> T on hearing, and show that this mutation can be found in different Caucasian mitochondrial DNA backgrounds.