Progressive External Ophthalmoplegia in Southwestern Finland: A Clinical and Genetic Study

Abstract

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.

Peripheral neuropathy predicts nuclear gene defect in patients with mitochondrial ophthalmoplegia

“…The main findings of this study are: (i) the most common genetic defect associated with PEO in patients with mitochondrial disease is a single mitochondrial DNA deletion, in line with previous studies (Zeviani et al , 1988; Holt et al , 1989; Moraes et al , 1989; Rodríguez-Hernández et al , 2000; Jiménez Caballero et al , 2007; Martikainen et al , 2012); (ii) peripheral neuropathy is a rare clinical feature in patients with a single mitochondrial DNA deletion; and (iii) in the present patient sample, among several individual clinical features, peripheral neuropathy was the most important in predicting the genetic defect in patients with PEO caused by mitochondrial disease, followed by family history and hearing loss.…”

“…Second, this was a single-centre study and the sample might not be representative of the whole patient population. However, the frequency distribution of genotypes among patients with PEO is similar to that observed in other case series (Holt et al , 1989; Jackson et al , 1995; Rodríguez-Hernández et al , 2000), studies based on single-centre experience (Jiménez Caballero et al , 2007), and population-based studies (Martikainen et al , 2012). In addition, to minimize selection biases, all patients with PEO and mitochondrial disease that were assessed at our centre and with clinical information available were included in the study.…”

Incidence and prevalence of mtDNA-related adult mitochondrial disease in Southwest Finland, 2009–2022: an observational, population-based study

“…Multiplex ligation-dependent probe amplification analysis was used for the detection of large mtDNA deletions. Some patients had been identified during previous research on mitochondrial disease epidemiology at the University of Turku 6–8. Only diagnoses of established pathogenic variants were included.…”

“…Some patients had been identified during previous research on mitochondrial disease epidemiology at the University of Turku. [6][7][8] Only diagnoses of established pathogenic variants were included.…”