Optimization of the Y831C mutation detection in human DNA polymerase gamma by allelic discrimination assay.

Stopińska, Katarzyna; Grzybowski, Tomasz; Malyarchuk, B. A.; Derenko, Miroslava; Miścicka-Śliwka, Danuta

doi:10.18388/abp.2006_3332

Cited by 10 publications

(6 citation statements)

References 24 publications

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“…Neither patient #3 nor her mother exhibited signs of Parkinsonism, features that have previously been reported with dominant expression of this variant . Moreover, it has been found at a high percentage in control populations, most notably in a Polish population (2.25%) . The recent findings of Wong et al .…”

Section: Discussionmentioning

confidence: 78%

“…27,28 Moreover, it has been found at a high percentage in control populations, most notably in a Polish population (2.25%). [29][30][31] The recent findings of Wong et al and Tang et al also indicate that p.Y831C is a neutral polymorphism even though its incidence in patients exhibiting symptoms suggestive of POLG-related diseases was high in these studies.…”

Section: Prevalence Of Polg Mutationsmentioning

confidence: 85%

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POLG mutations in Australian patients with mitochondrial disease

Woodbridge

Liang

Davis

et al. 2013

Internal Medicine Journal

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Section: Discussionmentioning

confidence: 78%

Section: Prevalence Of Polg Mutationsmentioning

confidence: 85%

POLG mutations in Australian patients with mitochondrial disease

Woodbridge

Liang

Davis

et al. 2013

Internal Medicine Journal

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“…Y831C is located very close to motif A in the polymerase region of POLG and has previously been reported in a family with PEO, peripheral neuropathy and Parkinsonism, but not in controls (Mancuso et al., ), pointing toward a pathogenic role. However, it has been found at a high percentage in control populations (Barthelemy et al., ; Stopinska et al., ; Tiangyou et al., ). The recent findings of Wong et al () and Woodbridge et al () also indicated that Y831C is a neutral polymorphism in spite of its incidence in patients exhibiting symptoms suggestive of POLG‐related diseases (Wong et al., ; Woodbridge et al., ).…”

Section: Discussionmentioning

confidence: 99%

“…SNP rs2307441, insertion GTAG in intron 17 (rs2307433) and nucleotide variant c.2481–7C>T were genotyped using Custom TaqMan® SNP Genotyping Assay according to the manufacturer's instructions. Mutation Y831C was genotyped as described by Stopińska et al ().…”

Section: Methodsmentioning

confidence: 99%

Mitochondrial DNA Polymerase γ Mutations and Their Implications in mtDNA Alterations in Colorectal Cancer

Linkowska

Jawień

Marszałek

et al. 2015

Annals of Human Genetics

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SummaryMitochondrial DNA was found to be highly mutated in colorectal cancer cells. One of the key molecules involved in the maintenance of the mitochondrial genome is the nuclear-encoded polymerase gamma. The aim of our study was to determine if there is a link between polymorphisms within the polymerase gamma gene (POLG) and somatic mutations within the mitochondrial genome in cancer cells. We investigated POLG sequence variability in 50 colorectal cancer patients whose complete mitochondrial genome sequences were determined. Relative mtDNA copy number was also determined. We identified 251 sequence variants in the POLG gene. Most of them were germline-specific (ß92%). Twenty-one somatic changes in POLG were found in 10 colorectal cancer patients. We have found no association between the occurrence of mtDNA somatic mutations and the somatically occurring variants in POLG. MtDNA content was reduced in patients carrying somatic variants in POLG or germline nucleotide variants located in the region encoding the POLG polymerase domain, but the difference did not reach statistical significance. Our findings suggest that somatic mtDNA mutations occurring in colorectal cancer are not a consequence of somatic mutations in POLG. Nevertheless, POLG nucleotide variants may lead to a decrease in mtDNA content, and consequently result in mitochondrial dysfunction.

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“…Finally, Mancuso et al [ 25 ] reported a proband and her brother with the heterozygous Y831C mutation that presented with parkinsonism and PEO. However, the pathogenic role of this mutation is still unclear; indeed, although the Y831C mutation has been observed in heterozygous or compound heterozygous conditions in both infantile and late-onset cases with variable phenotypes, it has also been shown to be present at a high frequency in healthy controls [ 26 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

The Y831C Mutation of the POLG Gene in Dementia

et al. 2023

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Background: The POLG gene encodes the catalytic subunit of DNA polymerase γ, which is crucial for mitochondrial DNA (mtDNA) repair and replication. Gene mutation alters the stability of mtDNA and is associated with several clinical presentations, such as dysarthria and ophthalmoplegia (SANDO), progressive external ophthalmoplegia (PEO), spinocerebellar ataxia and epilepsy (SCAE), Alpers syndrome, and sensory ataxic neuropathy. Recent evidence has also indicated that POLG mutations may be involved in some neurodegenerative disorders, although systematic screening is currently lacking. Methods: To investigate the frequency of POLG gene mutations in neurodegenerative disorders, we screened a group of 33 patients affected by neurodegenerative diseases, including Parkinson’s disease, some atypical parkinsonisms, and dementia of different types. Results: Mutational analysis revealed the presence of the heterozygous Y831C mutation in two patients, one with frontotemporal dementia and one with Lewy body dementia. The allele frequency of this mutation reported by the 1000 Genomes Project in the healthy population is 0.22%, while in our group of patients, it was 3.03%, thus showing a statistically significant difference between the two groups. Conclusions: Our results may expand the genotype-phenotype spectrum associated with mutations in the POLG gene and strengthen the hypothesis of a pathogenic role of the Y831C mutation in neurodegeneration.

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Optimization of the Y831C mutation detection in human DNA polymerase gamma by allelic discrimination assay.

Cited by 10 publications

References 24 publications

POLG mutations in Australian patients with mitochondrial disease

POLG mutations in Australian patients with mitochondrial disease

Mitochondrial DNA Polymerase γ Mutations and Their Implications in mtDNA Alterations in Colorectal Cancer

The Y831C Mutation of the POLG Gene in Dementia

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