Department of Neurology, Turku University Hospital, Turku, Finland.
Neuroepidemiology. 2012;38(2):114-9. doi: 10.1159/000336112. Epub 2012 Feb 24.
Progressive external ophthalmoplegia (PEO) is a common phenotype of mitochondrial disease. Molecular etiologies include sporadic, large-scale deletions in mitochondrial DNA (mtDNA), multiple mtDNA deletions secondary to autosomal dominant or recessive mutations and mtDNA point mutations.
We studied the prevalence and clinical and genetic characteristics of PEO in a defined population in southwestern Finland. A total of 620 patients were first identified from the patient registry at the Turku University Hospital over an 18-year period. The medical records of these patients were scrutinized, and those with clinical features compatible with PEO were ascertained.
We identified 10 patients with possible PEO. The patients were examined clinically, and DNA was analyzed for mtDNA deletions and for the m.3243A>G and m.8344A>G mtDNA point mutations. The ANT1, PEO1, POLG1 and POLG2 genes were sequenced. We confirmed the clinical diagnosis of PEO in 6 patients. Large-scale mtDNA deletions were detected in 3 out of 6 PEO patients and mutations in the POLG1 gene in 1 out of 6. We did not find any mutations in the ANT1, PEO1 or POLG2 genes.
Our results suggest that molecular investigation of patients with PEO, either sporadic or familial, should start with an analysis for mtDNA deletions, followed by an analysis of the POLG1 gene.
进行性眼外肌麻痹（PEO）是线粒体疾病的常见表型。分子病因包括散发性、线粒体 DNA（mtDNA）的大片段缺失、常染色体显性或隐性突变引起的多个 mtDNA 缺失以及 mtDNA 点突变。
我们在芬兰西南部的一个特定人群中研究了 PEO 的患病率以及临床和遗传特征。在 18 年的时间里，我们首次从图尔库大学医院的患者登记处确定了 620 名患者。仔细检查了这些患者的病历，并确定了那些具有与 PEO 相符的临床特征的患者。
我们确定了 10 名可能患有 PEO 的患者。对患者进行了临床检查，并对 mtDNA 缺失以及 m.3243A>G 和 m.8344A>G mtDNA 点突变进行了 DNA 分析。对 ANT1、PEO1、POLG1 和 POLG2 基因进行了测序。我们在 6 名患者中确认了 PEO 的临床诊断。在 6 名 PEO 患者中有 3 名检测到大片段 mtDNA 缺失，有 1 名患者检测到 POLG1 基因突变。我们在 ANT1、PEO1 或 POLG2 基因中未发现任何突变。
我们的结果表明，无论是散发性还是家族性 PEO 患者，分子研究都应首先进行 mtDNA 缺失分析，然后进行 POLG1 基因分析。
