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Abstract
Mitochondrial dysfunction is known to play a key role in the pathophysiological pathway of neurodegenerative disorders. Nuclear-encoded proteins are involved in mtDNA replication, including DNA polymerase gamma, which is the only known replicative mtDNA polymerase, encoded by nuclear genes Polymerase gamma 1 (POLG) and Polymerase gamma 2 (POLG2). POLG mutations are well-known as a frequent cause of mitochondrial myopathies of nuclear origin. However, only rare descriptions of POLG2 mutations leading to mitochondriopathies exist. Here we describe a 68-year-old woman presenting with a 20-year history of camptocormia, mild proximal weakness, and moderate CK increase. Muscle histology showed COX-negative fibres. Genetic analysis by next generation sequencing revealed an already reported heterozygous c.1192-8_1207dup24 mutation in the POLG2 gene. This is the first report on a POLG2 mutation leading to camptocormia as the main clinical phenotype, extending the phenotypic spectrum of POLG2 associated diseases. This underlines the broad phenotypic spectrum found in mitochondrial diseases, especially in mitochondrial disorders of nuclear origin.
Highlights
Mitochondrial diseases are associated with a wide spectrum of different clinical phenotypes, ranging from mild to severe [1]
Genetic analysis by generation sequencing revealed an already reported heterozygous c.1192-8_1207dup24 mutation in the Polymerase gamma 2 (POLG2) gene. This is the first report on a POLG2 mutation leading to camptocormia as the main clinical phenotype, extending the phenotypic spectrum of POLG2 associated diseases
Those required for mitochondrial DNA (mtDNA) replication (POLG and TWNK) [2]. mtDNA replication is accomplished by DNA polymerase gamma, a heterotrimer consisting of one catalytic subunit of DNA polymerase encoded by Polymerase gamma 1 (POLG) and a dimer of accessory subunits encoded by POLG2, a processivity factor for the DNA polymerase [3,4,5]
Summary
Mitochondrial diseases are associated with a wide spectrum of different clinical phenotypes, ranging from mild to severe [1]. They can either be caused by mutations in the mitochondrial DNA (mtDNA) itself or due to mutations of nuclear origin: (I) nuclear genes encoding for enzymes involved in mitochondrial nucleotide synthesis (TK2, SUCLA2, SUCLG1, RRM2B, DGUOK, and TYMP) or (II). Those required for mtDNA replication (POLG and TWNK) [2].
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