Epidemiology of A3243G, the mutation for mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes:: Prevalence of the mutation in an adult population
Epidemiology of A3243G, the mutation for mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes:: Prevalence of the mutation in an adult population
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DOI：
10.1086/301959
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发表时间：
1998-08-01
影响因子：
9.8
通讯作者：
Hassinen, IE
中科院分区：
文献类型：
--
作者：
Majamaa, K;Moilanen, JS;Hassinen, IE
线粒体疾病的特征在于相当大的临床变异性，并且最常由mtDNA突变引起。由于表型的变异性，这些疾病的发生频率的流行病学研究一直难以进行。我们研究了245，201例成年人群中mtDNA 3243位核苷酸突变的患病率。这种突变是MELAS综合征（线粒体脑肌病、乳酸酸中毒和卒中样发作）最常见的分子病因，MELAS综合征是线粒体疾病中的临床实体之一。糖尿病、感觉神经性听力障碍、癫痫、枕叶脑梗死、眼肌麻痹、脑白质疾病、基底节钙化、肥厚型心肌病或共济失调患者根据明确的临床标准和家族史资料确定。总共确定了615名患者，并检查了480个样本的突变。在11个家系中发现了该突变，其频率在成年人群中计算为大于或等于16.3/10万（95%置信区间11.3-21.4/10万）。根据mtDNA单倍型分析，该突变在人群中至少发生了9次。先证者的临床评估显示，最常见的综合征包括听力障碍、认知能力下降和身材矮小。常见的MELAS突变在成年人群中的高患病率表明，线粒体疾病构成了神经遗传性疾病的最大诊断类别之一。
Mitochondrial diseases are characterized by considerable clinical variability and are most often caused by mutations in mtDNA. Because of the phenotypic variability, epidemiological studies of the frequency of these disorders have been difficult to perform. We studied the prevalence of the mtDNA mutation at nucleotide 3243 in an adult population of 245,201 individuals. This mutation is the most common molecular etiology of MELAS syndrome (mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes), one of the clinical entities among the mitochondrial disorders. Patients with diabetes mellitus, sensorineural hearing impairment, epilepsy, occipital brain infarct, ophthalmoplegia, cerebral white-matter disease, basal-ganglia calcifications, hypertrophic cardiomyopathy, or ataxia were ascertained on the basis of defined clinical criteria and family-history data. A total of 615 patients were identified, and 480 samples were examined for the mutation. The mutation was found in 11 pedigrees, and its frequency was calculated to be greater than or equal to 16.3/100,000 in the adult population (95% confidence interval 11.3-21.4/100,000). The mutation had arisen in the population at least nine times, as determined by mtDNA haplotyping. Clinical evaluation of the probands revealed a syndrome that most frequently consisted of hearing impairment, cognitive decline, and short stature. The high prevalence of the common MELAS mutation in the adult population suggests that mitochondrial disorders constitute one of the largest diagnostic categories of neurogenetic diseases.