Mutation of POLG is associated with progressive external ophthalmoplegia characterized by mtDNA deletions

@article{Goethem2001MutationOP,
  title={Mutation of POLG is associated with progressive external ophthalmoplegia characterized by mtDNA deletions},
  author={Geert van Goethem and Bart Dermaut and Ann L{\"o}fgren and Jean-Jacques Martin and Christine Van Broeckhoven},
  journal={Nature Genetics},
  year={2001},
  volume={28},
  pages={211-212}
}
Progressive external ophthalmoplegias (PEO) characterized by accumulation of large-scale mitochondrial DNA (mtDNA) deletions are rare human diseases. We mapped a new locus for dominant PEO at 15q22-q26 in a Belgian pedigree and identified a heterozygous mutation (Y955C) in the polymerase motif B of the mtDNA polymerase γ (POLG). We identified three additional POLG missense mutations compatible with recessive PEO In two nuclear families. POLG is the only DNA polymerase responsible for mtDNA… 
Clinical and Genetic Heterogeneity in Progressive External Ophthalmoplegia Due to Mutations in Polymerase 3
Background: The mendelian forms of progressive external ophthalmoplegia (PEO) associated with multiple mitochondrial DNA deletions are clinically heterogeneous disorders transmitted as dominant or
Mutations of mitochondrial DNA polymerase γA are a frequent cause of autosomal dominant or recessive progressive external ophthalmoplegia
TLDR
Data show that mutations of POLG1 are the most frequent cause of familial progressive external ophthalmoplegia associated with accumulation of multiple mitochondrial DNA deletions, accounting for approximately 45% of the family cohort.
Novel POLG mutations in progressive external ophthalmoplegia mimicking mitochondrial neurogastrointestinal encephalomyopathy
TLDR
A recessive family with features of MNGIE but no leukoencephalopathy is reported in which two patients carry three missense mutations in POLG, of which two are novel mutations (N846S and P587L).
Progressive external ophthalmoplegia and multiple mitochondrial DNA deletions.
TLDR
This work identified POLG mutations in two families with arPEO, which underlines the crucial role of the mtDNA replication machinery for mtDNA maintenance.
A novel Twinkle gene mutation in autosomal dominant progressive external ophthalmoplegia
TLDR
A family with autosomal dominant progressive external ophthalmoplegia is described, caused by a novel heterozygous A to C transversion at nucleotide 956 of the Twinkle gene.
Clinical and genetic heterogeneity in progressive external ophthalmoplegia due to mutations in polymerase gamma.
TLDR
It is demonstrated that POLG mutations account for a substantial proportion of patients with PEO and multiple mitochondrial DNA deletions and cause both clinically and genetically heterogeneous disorders.
POLG1, C10ORF2, and ANT1 mutations are uncommon in sporadic progressive external ophthalmoplegia with multiple mitochondrial DNA deletions
TLDR
The authors sequenced POLG1, C10ORF2, and ANT1 in 38 sporadic progressive external ophthalmoplegia patients with multiple mitochondrial DNA (mtDNA) deletions, finding that in the majority of patients, the primary nuclear genetic defect is likely to affect other unknown genes important for mtDNA maintenance.
Progressive external ophthalmoplegia characterized by multiple deletions of mitochondrial DNA
TLDR
It is advocated the use of a genetic, instead of a clinical, classification of disorders with multiple mtDNA deletions, since clinical presentations are heterogeneous and overlap with different previously described clinical syndromes.
Patient homozygous for a recessive POLG mutation presents with features of MERRF
TLDR
A patient homozygous for a recessive missense mutation in POLG who presented with a multisystem disorder without PEO, so the clinical picture overlapped with the syndrome of myoclonus, epilepsy, and ragged red fibers (MERRF).
Thymidine kinase 2 mutations in autosomal recessive progressive external ophthalmoplegia with multiple mitochondrial DNA deletions.
Autosomal-inherited progressive external ophthalmoplegia (PEO) is an adult-onset disease characterized by the accumulation of multiple mitochondrial DNA (mtDNA) deletions in post-mitotic tissues.
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