D-loop mutations in mitochondrial DNA:: link with mitochondrial DNA depletion?
D-loop mutations in mitochondrial DNA:: link with mitochondrial DNA depletion?
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DOI：
10.1007/s00439-002-0708-4
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发表时间：
2002-05-01
期刊：
影响因子：
5.3
通讯作者：
Lombès, A
中科院分区：
文献类型：
--
作者：
Barthélémy, C;de Baulny, HO;Lombès, A
线粒体DNA缺失患者的临床表现相当多样，提示存在遗传异质性。常染色体隐性遗传可能是该病的原因，因此暗示了该病的核起源。最近在有新生儿症状的大家庭中证明了这一点。在这里，我们报告了一个有一个孩子的家庭，患有与严重的线粒体DNA耗竭相关的晚发性疾病。患者母亲肌肉中线粒体的变化促使我们广泛分析了这家人的线粒体DNA。我们发现了线粒体DNA的多个缺失，但也发现了D-loop区域的三个异质点突变，其中两个(T119C和T408A)影响了参与mtDNA复制过程的保守区。这些突变在母系中非随机分布，其中一种是在单个肌肉纤维中。因此，线粒体DNA自身的耗尽似乎是可能的。它的作用可能与一种假想的修饰核因子密切相关。
Clinical presentation of the patients with mitochondrial DNA depletion is quite diverse and is suggestive of genetic heterogeneity. Autosomal recessive inheritance of the disease appears likely, thus implying the nuclear origin of the disease. This has been demonstrated recently in large families with neonatal presentation of the disease. Here, we report upon a family with one child having a late-onset disease associated with severe mitochondrial DNA depletion. The presence of mitochondrial alterations in the muscle of the patient's mother prompted us to extensively analyse the mitochondrial DNA in the family. We found mitochondrial DNA multiple deletions, but also three heteroplasmic point mutations of the D-loop region, two of which (T119C and T408A) affect conserved regions involved in the mtDNA replication process. These mutations were non-randomly distributed in the maternal lineage and, for one of them, among single muscle fibres. Involvement of the mitochondrial DNA in its own depletion appears therefore possible. It may act in close relationship with a hypothetical modified nuclear factor.