Abstract
Mitochondrial encephalomyopathies comprise a group of heterogeneous disorders resulting from impaired oxidative phosphorylation (OxPhos). Among a variety of symptoms progressive external ophthalmoplegia (PEO) seems to be the most common. The aim of this study is to present clinical and genetic characteristics of Polish patients with PEO. Clinical, electrophysiological, neuroradiological, and morphological data of 84 patients were analyzed. Genetic studies of mitochondrial DNA (mtDNA) were performed in all patients. Among nuclear DNA (nDNA) genes POLG was sequenced in 41 patients, TWNK (C10orf2) in 13 patients, and RNASEH1 in 2 patients. Total of 27 patients were included in the chronic progressive external ophthalmoplegia (CPEO) group, 24 in the CPEO+ group. Twenty-six patients had mitochondrial encephalomyopathy (ME), six patients Kearns-Sayre syndrome (KSS), and one patient sensory ataxic neuropathy, dysarthria, ophthalmoparesis (SANDO) syndrome. Genetic analysis of nDNA genes revealed the presence of pathogenic or possibly pathogenic variants in the POLG gene in nine patients, the TWNK gene in five patients and the RNASEH1 gene in two patients. Detailed patients' history and careful assessment of family history are essential in the diagnostic work-up. Genetic studies of both mtDNA and nDNA are necessary for the final diagnosis of progressive external ophthalmoplegia and for genetic counseling.
Keywords:
POLG gene; RNASEH1 gene; TWNK gene; mitochondrial DNA deletions; mitochondrial disorders; multiple mitochondrial DNA deletions; muscle biopsy; progressive external ophthalmoplegia.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adolescent
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Adult
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Aged
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Cerebellum / diagnostic imaging
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Cerebellum / metabolism
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Cerebellum / pathology
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Cerebrum / diagnostic imaging
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Cerebrum / metabolism
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Cerebrum / pathology
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Child
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DNA Helicases / genetics*
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DNA Helicases / metabolism
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DNA Polymerase gamma / genetics*
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DNA Polymerase gamma / metabolism
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DNA, Mitochondrial / genetics
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DNA, Mitochondrial / metabolism
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Diagnosis, Differential
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Female
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Gene Expression
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Humans
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Kearns-Sayre Syndrome / diagnostic imaging
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Kearns-Sayre Syndrome / genetics*
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Kearns-Sayre Syndrome / metabolism
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Kearns-Sayre Syndrome / pathology
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Male
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Middle Aged
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Mitochondria / metabolism
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Mitochondria / pathology
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Mitochondrial Diseases / diagnostic imaging
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Mitochondrial Diseases / genetics*
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Mitochondrial Diseases / metabolism
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Mitochondrial Diseases / pathology
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Mitochondrial Encephalomyopathies / diagnostic imaging
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Mitochondrial Encephalomyopathies / genetics*
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Mitochondrial Encephalomyopathies / metabolism
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Mitochondrial Encephalomyopathies / pathology
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Mitochondrial Proteins / genetics*
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Mitochondrial Proteins / metabolism
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Muscle, Skeletal / metabolism
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Muscle, Skeletal / pathology
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Ophthalmoplegia, Chronic Progressive External / diagnostic imaging
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Ophthalmoplegia, Chronic Progressive External / genetics*
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Ophthalmoplegia, Chronic Progressive External / metabolism
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Ophthalmoplegia, Chronic Progressive External / pathology
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Pedigree
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Poland
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Polymorphism, Genetic
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Ribonuclease H / genetics*
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Ribonuclease H / metabolism
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Sequence Deletion
Substances
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DNA, Mitochondrial
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Mitochondrial Proteins
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DNA Polymerase gamma
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POLG protein, human
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Ribonuclease H
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ribonuclease HI
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DNA Helicases
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TWNK protein, human
Supplementary concepts
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Ataxia Neuropathy Spectrum