Progressive external ophthalmoplegia in southwestern Finland: A clinical and genetic study

摘要

Background: Progressive external ophthalmoplegia (PEO) is a common phenotype of mitochondrial disease. Molecu- lar etiologies include sporadic, large-scale deletions in mitochondrial DNA (mtDNA), multiple mtDNA deletions secondary to autosomal dominant or recessive mutations and mtDNA point mutations. Methods: 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. Results: 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. Conclusions: 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.