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De Novo Development of mtDNA Deletion Due to Decreased POLG and SSBP1 Expression in Humans

Defects in the mitochondrial genome (mitochondrial DNA (mtDNA)) are associated with both congenital and acquired disorders in humans. Nuclear-encoded DNA polymerase subunit gamma (POLG) plays an important role in mtDNA replication, and proofreading and mutations in POLG have been linked with increas...

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Autores principales: Lee, Yeonmi, Kim, Taeho, Lee, Miju, So, Seongjun, Karagozlu, Mustafa Zafer, Seo, Go Hun, Choi, In Hee, Lee, Peter C. W., Kim, Chong-Jai, Kang, Eunju, Lee, Beom Hee
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922481/
https://www.ncbi.nlm.nih.gov/pubmed/33671400
http://dx.doi.org/10.3390/genes12020284
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author Lee, Yeonmi
Kim, Taeho
Lee, Miju
So, Seongjun
Karagozlu, Mustafa Zafer
Seo, Go Hun
Choi, In Hee
Lee, Peter C. W.
Kim, Chong-Jai
Kang, Eunju
Lee, Beom Hee
author_facet Lee, Yeonmi
Kim, Taeho
Lee, Miju
So, Seongjun
Karagozlu, Mustafa Zafer
Seo, Go Hun
Choi, In Hee
Lee, Peter C. W.
Kim, Chong-Jai
Kang, Eunju
Lee, Beom Hee
author_sort Lee, Yeonmi
collection PubMed
description Defects in the mitochondrial genome (mitochondrial DNA (mtDNA)) are associated with both congenital and acquired disorders in humans. Nuclear-encoded DNA polymerase subunit gamma (POLG) plays an important role in mtDNA replication, and proofreading and mutations in POLG have been linked with increased mtDNA deletions. SSBP1 is also a crucial gene for mtDNA replication. Here, we describe a patient diagnosed with Pearson syndrome with large mtDNA deletions that were not detected in the somatic cells of the mother. Exome sequencing was used to evaluate the nuclear factors associated with the patient and his family, which revealed a paternal POLG mutation (c.868C > T) and a maternal SSBP1 mutation (c.320G > A). The patient showed lower POLG and SSBP1 expression than his healthy brothers and the general population of a similar age. Notably, c.868C in the wild-type allele was highly methylated in the patient compared to the same site in both his healthy brothers. These results suggest that the co- deficient expression of POLG and SSBP1 genes could contribute to the development of mtDNA deletion.
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spelling pubmed-79224812021-03-03 De Novo Development of mtDNA Deletion Due to Decreased POLG and SSBP1 Expression in Humans Lee, Yeonmi Kim, Taeho Lee, Miju So, Seongjun Karagozlu, Mustafa Zafer Seo, Go Hun Choi, In Hee Lee, Peter C. W. Kim, Chong-Jai Kang, Eunju Lee, Beom Hee Genes (Basel) Article Defects in the mitochondrial genome (mitochondrial DNA (mtDNA)) are associated with both congenital and acquired disorders in humans. Nuclear-encoded DNA polymerase subunit gamma (POLG) plays an important role in mtDNA replication, and proofreading and mutations in POLG have been linked with increased mtDNA deletions. SSBP1 is also a crucial gene for mtDNA replication. Here, we describe a patient diagnosed with Pearson syndrome with large mtDNA deletions that were not detected in the somatic cells of the mother. Exome sequencing was used to evaluate the nuclear factors associated with the patient and his family, which revealed a paternal POLG mutation (c.868C > T) and a maternal SSBP1 mutation (c.320G > A). The patient showed lower POLG and SSBP1 expression than his healthy brothers and the general population of a similar age. Notably, c.868C in the wild-type allele was highly methylated in the patient compared to the same site in both his healthy brothers. These results suggest that the co- deficient expression of POLG and SSBP1 genes could contribute to the development of mtDNA deletion. MDPI 2021-02-17 /pmc/articles/PMC7922481/ /pubmed/33671400 http://dx.doi.org/10.3390/genes12020284 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lee, Yeonmi
Kim, Taeho
Lee, Miju
So, Seongjun
Karagozlu, Mustafa Zafer
Seo, Go Hun
Choi, In Hee
Lee, Peter C. W.
Kim, Chong-Jai
Kang, Eunju
Lee, Beom Hee
De Novo Development of mtDNA Deletion Due to Decreased POLG and SSBP1 Expression in Humans
title De Novo Development of mtDNA Deletion Due to Decreased POLG and SSBP1 Expression in Humans
title_full De Novo Development of mtDNA Deletion Due to Decreased POLG and SSBP1 Expression in Humans
title_fullStr De Novo Development of mtDNA Deletion Due to Decreased POLG and SSBP1 Expression in Humans
title_full_unstemmed De Novo Development of mtDNA Deletion Due to Decreased POLG and SSBP1 Expression in Humans
title_short De Novo Development of mtDNA Deletion Due to Decreased POLG and SSBP1 Expression in Humans
title_sort de novo development of mtdna deletion due to decreased polg and ssbp1 expression in humans
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922481/
https://www.ncbi.nlm.nih.gov/pubmed/33671400
http://dx.doi.org/10.3390/genes12020284
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