Hansrote Sun, Croul Sidney, Selak Mary, Kalman Bernadette, Schwartzman Robert J
Department of Neurology, MCP Hahnemann University, MS 423, 245 North 15th Street, Philadelphia, PA 19102, USA.
J Neurol Sci. 2002 May 15;197(1-2):63-7. doi: 10.1016/s0022-510x(02)00048-5.
Chronic progressive external ophthalmoplegia (CPEO) may be related to primary nuclear DNA or mitochondrial (mt)DNA mutations. The A3243G mtDNA point mutation most frequently causes mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome, but also has been associated with other phenotypes including CPEO, migraine, seizure, diabetes, and sensorineural hearing loss.
We report a 38-year-old white man with seizures and progressive difficulties of infantile origin including CPEO, sensorineural hearing loss, cataracts, migraines, multiple endocrinopathy, myopathy, and cardiomyopathy. Moderate hearing loss in association with CPEO, diabetes mellitus, or migraines were noted in the proband's maternal grandmother, great aunt, mother, and three sisters, suggesting either an autosomal dominant or maternal inheritance. Detailed histological and biochemical analysis of the proband's biopsied muscle specimen revealed severe abnormalities compatible with a mitochondrial disease. MtDNA analysis excluded large-scale deletions, but revealed a heteroplasmic A to G transition at nt3243 in 56.4% and 27.4% of molecules in muscle and white blood cells, respectively.
We discuss possible causes of this intrafamilial heterogeneity of phenotypes associated with the A3243G mtDNA mutation.
慢性进行性眼外肌麻痹（CPEO）可能与原发性核DNA或线粒体（mt）DNA突变有关。A3243G mtDNA点突变最常导致线粒体脑病、乳酸性酸中毒和卒中样发作（MELAS）综合征，但也与包括CPEO、偏头痛、癫痫、糖尿病和感音神经性听力损失在内的其他表型有关。
我们报告一名38岁白人男性，患有癫痫以及自幼起病的进行性疾病，包括CPEO、感音神经性听力损失、白内障、偏头痛、多发性内分泌病、肌病和心肌病。先证者的外祖母、姨祖母、母亲和三个姐妹存在与CPEO、糖尿病或偏头痛相关的中度听力损失，提示可能为常染色体显性遗传或母系遗传。对先证者活检肌肉标本进行详细的组织学和生化分析，发现严重异常，符合线粒体疾病。mtDNA分析排除了大规模缺失，但在肌肉和白细胞中分别有56.4%和27.4%的分子检测到nt3243处A到G的异质性转变。
我们讨论了与A3243G mtDNA突变相关的家系内表型异质性的可能原因。
