Prevalence of nuclear and mitochondrial DNA mutations related to adult mitochondrial disease.
Prevalence of nuclear and mitochondrial DNA mutations related to adult mitochondrial disease.
复制标题
与成年线粒体疾病有关的核和线粒体DNA突变的患病率。
DOI：
10.1002/ana.24362
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发表时间：
2015-05
影响因子：
11.2
通讯作者：
McFarland R
中科院分区：
文献类型：
--
作者：
Gorman GS;Schaefer AM;Ng Y;Gomez N;Blakely EL;Alston CL;Feeney C;Horvath R;Yu-Wai-Man P;Chinnery PF;Taylor RW;Turnbull DM;McFarland R
线粒体疾病的流行已被证明很难确定，主要是由于临床和遗传异质性的结果。自从最初报道与线粒体DNA(MtDNA)重排和点突变相关的经典临床症状以来，线粒体疾病的表型谱显著扩大。基因技术的革命使对核基因组的询问成为可能，极大地改善了线粒体疾病的诊断。我们全面评估了所有形式的成人线粒体疾病的患病率，包括核和线粒体DNA的致病突变。从1990年到2014年，英格兰东北部疑似线粒体疾病的成年人被转诊到一个神经学中心。在2011年年中期间，我们评估了导致线粒体疾病的症状性核DNA突变以及症状性和无症状性线粒体DNA突变的最低流行率。线粒体DNA突变的最低患病率为每5000人中有1人(每10万人中有20人)，与我们之前公布的患病率相当。在这一人群中，每100,000名成年人中有2.9人临床表现为线粒体疾病，其原因是核突变。综上所述，我们的数据证实，成人线粒体疾病的总患病率，包括线粒体和核基因组的致病突变(4,300人中有1例≈)，是最常见的成人遗传性神经疾病形式之一。这些数字对评估干预措施、提供循证卫生政策和规划未来服务具有重要意义。Ann Neurol 2015 Ann Neurol 2015；77：753-759
The prevalence of mitochondrial disease has proven difficult to establish, predominantly as a result of clinical and genetic heterogeneity. The phenotypic spectrum of mitochondrial disease has expanded significantly since the original reports that associated classic clinical syndromes with mitochondrial DNA (mtDNA) rearrangements and point mutations. The revolution in genetic technologies has allowed interrogation of the nuclear genome in a manner that has dramatically improved the diagnosis of mitochondrial disorders. We comprehensively assessed the prevalence of all forms of adult mitochondrial disease to include pathogenic mutations in both nuclear and mtDNA. Adults with suspected mitochondrial disease in the North East of England were referred to a single neurology center from 1990 to 2014. For the midyear period of 2011, we evaluated the minimum prevalence of symptomatic nuclear DNA mutations and symptomatic and asymptomatic mtDNA mutations causing mitochondrial diseases. The minimum prevalence rate for mtDNA mutations was 1 in 5,000 (20 per 100,000), comparable with our previously published prevalence rates. In this population, nuclear mutations were responsible for clinically overt adult mitochondrial disease in 2.9 per 100,000 adults. Combined, our data confirm that the total prevalence of adult mitochondrial disease, including pathogenic mutations of both the mitochondrial and nuclear genomes (≈1 in 4,300), is among the commonest adult forms of inherited neurological disorders. These figures hold important implications for the evaluation of interventions, provision of evidence‐based health policies, and planning of future services. Ann Neurol 2015 Ann Neurol 2015;77:753–759