Melberg A, Arnell H, Dahl N, Stålberg E, Raininko R, Oldfors A, Bakall B, Lundberg P O, Holme E
Department of Neurology, University Hospital, Uppsala, Sweden.
Muscle Nerve. 1996 Dec;19(12):1561-9. doi: 10.1002/(SICI)1097-4598(199612)19:12<1561::AID-MUS5>3.0.CO;2-8.
A large Swedish family with members affected by progressive external ophthalmoplegia with hypogonadism were followed-up and reviewed. Hypogonadism included delayed sexual maturation, primary amenorrhea, early menopause, and testicular atrophy. Cataracts, cerebellar ataxia, neuropathy, hypoacusia, pes cavus, tremor, parkinsonism, depression, and mental retardation were other features observed in this family. Muscle biopsy samples of advanced cases showed ragged-red fibers, focal cytochrome c oxidase deficiency, and multiple mtDNA deletions by Southern blot analysis. An autosomal dominant mode of inheritance was evident with anticipation in successive generations. Linkage analysis excluded the chromosome 10q23.3-q24.3 region reported as being linked to the disease in a Finnish family with autosomal dominant progressive external ophthalmoplegia. We report for the first time clinical evidence for anticipation in a family with autosomal dominant progressive external ophthalmoplegia. We hypothesize that the nuclear gene causing this enigmatic disorder may be directly influenced by an expansion of an unstable DNA sequence and that the resulting phenotype is caused by a concerted action with multiple deletions of mtDNA.
对一个有成员患进行性眼外肌麻痹伴性腺功能减退的瑞典大家庭进行了随访和回顾。性腺功能减退包括性成熟延迟、原发性闭经、早绝经和睾丸萎缩。白内障、小脑共济失调、神经病变、听力减退、高弓足、震颤、帕金森症、抑郁和智力迟钝是在这个家庭中观察到的其他特征。晚期病例的肌肉活检样本显示有破碎红纤维、局灶性细胞色素c氧化酶缺乏以及通过Southern印迹分析发现多个线粒体DNA缺失。常染色体显性遗传模式明显，且在连续几代中有遗传早现现象。连锁分析排除了10q23.3 - q24.3染色体区域，该区域在一个患常染色体显性进行性眼外肌麻痹的芬兰家庭中被报道与该病相关。我们首次报道了一个常染色体显性进行性眼外肌麻痹家族中遗传早现的临床证据。我们推测，导致这种疑难病症的核基因可能直接受到不稳定DNA序列扩增的影响，并且由此产生的表型是由线粒体DNA的多个缺失共同作用引起的。
