Van Goethem Gert, Martin Jean-Jacques, Van Broeckhoven Christine
Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology (VIB-8), University of Antwerp (UIA).
Acta Neurol Belg. 2002 Mar;102(1):39-42.
Progressive external ophthalmoplegia (PEO) with secondary accumulation of multiple deletions of mitochondrial DNA (mtDNA) clinically resembles disorders due to primary mutations of mtDNA but follows a Mendelian inheritance pattern. The disorder belongs to an interesting group of diseases in which both the nuclear and the mitochondrial genome are involved in the pathology. Both autosomal dominant (adPEO) and recessive (arPEO) variants of this disorder occur. Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) patients may have multiple mtDNA deletions and/or depletion of mtDNA. Recent reports of mutations in Thymidine Phosphorylase in MNGIE, and of mutations in adenine nucleotide translocator (ANT1), Twinkle and mitochondrial DNA polymerase gamma (POLG) in adPEO, have lead to new insights in the pathogenesis of these disorders of mtDNA maintenance. We also identified POLG mutations in two families with arPEO, which underlines the crucial role of the mtDNA replication machinery for mtDNA maintenance.
进行性眼外肌麻痹（PEO）伴线粒体DNA（mtDNA）多次缺失的继发性蓄积，在临床上类似于由mtDNA原发性突变引起的疾病，但遵循孟德尔遗传模式。该疾病属于一组有趣的疾病，其中细胞核和线粒体基因组都参与了病理过程。该疾病存在常染色体显性（adPEO）和隐性（arPEO）两种变体。线粒体神经胃肠性脑肌病（MNGIE）患者可能存在多个mtDNA缺失和/或mtDNA耗竭。最近关于MNGIE中胸苷磷酸化酶突变以及adPEO中腺嘌呤核苷酸转位酶（ANT1）、Twinkle和线粒体DNA聚合酶γ（POLG）突变的报道，为这些mtDNA维持障碍的发病机制带来了新的见解。我们还在两个arPEO家族中鉴定出POLG突变，这强调了mtDNA复制机制对mtDNA维持的关键作用。
