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The Phenotypic Spectrum of 47 Czech Patients with Single, Large-Scale Mitochondrial DNA Deletions

Background: In this retrospective study, we analysed clinical, biochemical and molecular genetic data of 47 Czech patients with Single, Large-Scale Mitochondrial DNA Deletions (SLSMD). Methods: The diagnosis was based on the long-range PCR (LX-PCR) screening of mtDNA isolated from muscle biopsy in 1...

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Autores principales: Anteneová, Nicole, Kelifová, Silvie, Kolářová, Hana, Vondráčková, Alžběta, Tóthová, Iveta, Lišková, Petra, Magner, Martin, Zámečník, Josef, Hansíková, Hana, Zeman, Jiří, Tesařová, Markéta, Honzík, Tomáš
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690373/
https://www.ncbi.nlm.nih.gov/pubmed/33105723
http://dx.doi.org/10.3390/brainsci10110766
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author Anteneová, Nicole
Kelifová, Silvie
Kolářová, Hana
Vondráčková, Alžběta
Tóthová, Iveta
Lišková, Petra
Magner, Martin
Zámečník, Josef
Hansíková, Hana
Zeman, Jiří
Tesařová, Markéta
Honzík, Tomáš
author_facet Anteneová, Nicole
Kelifová, Silvie
Kolářová, Hana
Vondráčková, Alžběta
Tóthová, Iveta
Lišková, Petra
Magner, Martin
Zámečník, Josef
Hansíková, Hana
Zeman, Jiří
Tesařová, Markéta
Honzík, Tomáš
author_sort Anteneová, Nicole
collection PubMed
description Background: In this retrospective study, we analysed clinical, biochemical and molecular genetic data of 47 Czech patients with Single, Large-Scale Mitochondrial DNA Deletions (SLSMD). Methods: The diagnosis was based on the long-range PCR (LX-PCR) screening of mtDNA isolated from muscle biopsy in 15 patients, and from the buccal swab, urinary epithelial cells and blood in 32 patients. Results: A total of 57% patients manifested before the age of 16. We did not find any significant difference between paediatric and adult manifestation in either the proportion of patients that would develop extraocular symptoms, or the timespan of its progression. The survival rate in patients with Pearson Syndrome reached 60%. Altogether, five patients manifested with atypical phenotype not fulfilling the latest criteria for SLSMD. No correlation was found between the disease severity and all heteroplasmy levels, lengths of the deletion and respiratory chain activities in muscle. Conclusions: Paediatric manifestation of Progressive External Ophthalmoplegia (PEO) is not associated with a higher risk of multisystemic involvement. Contrary to PEO and Kearns-Sayre Syndrome Spectrum, Pearson Syndrome still contributes to a significant childhood mortality. SLSMD should be considered even in cases with atypical presentation. To successfully identify carriers of SLSMD, a repeated combined analysis of buccal swab and urinary epithelial cells is needed.
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spelling pubmed-76903732020-11-27 The Phenotypic Spectrum of 47 Czech Patients with Single, Large-Scale Mitochondrial DNA Deletions Anteneová, Nicole Kelifová, Silvie Kolářová, Hana Vondráčková, Alžběta Tóthová, Iveta Lišková, Petra Magner, Martin Zámečník, Josef Hansíková, Hana Zeman, Jiří Tesařová, Markéta Honzík, Tomáš Brain Sci Article Background: In this retrospective study, we analysed clinical, biochemical and molecular genetic data of 47 Czech patients with Single, Large-Scale Mitochondrial DNA Deletions (SLSMD). Methods: The diagnosis was based on the long-range PCR (LX-PCR) screening of mtDNA isolated from muscle biopsy in 15 patients, and from the buccal swab, urinary epithelial cells and blood in 32 patients. Results: A total of 57% patients manifested before the age of 16. We did not find any significant difference between paediatric and adult manifestation in either the proportion of patients that would develop extraocular symptoms, or the timespan of its progression. The survival rate in patients with Pearson Syndrome reached 60%. Altogether, five patients manifested with atypical phenotype not fulfilling the latest criteria for SLSMD. No correlation was found between the disease severity and all heteroplasmy levels, lengths of the deletion and respiratory chain activities in muscle. Conclusions: Paediatric manifestation of Progressive External Ophthalmoplegia (PEO) is not associated with a higher risk of multisystemic involvement. Contrary to PEO and Kearns-Sayre Syndrome Spectrum, Pearson Syndrome still contributes to a significant childhood mortality. SLSMD should be considered even in cases with atypical presentation. To successfully identify carriers of SLSMD, a repeated combined analysis of buccal swab and urinary epithelial cells is needed. MDPI 2020-10-22 /pmc/articles/PMC7690373/ /pubmed/33105723 http://dx.doi.org/10.3390/brainsci10110766 Text en © 2020 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
Anteneová, Nicole
Kelifová, Silvie
Kolářová, Hana
Vondráčková, Alžběta
Tóthová, Iveta
Lišková, Petra
Magner, Martin
Zámečník, Josef
Hansíková, Hana
Zeman, Jiří
Tesařová, Markéta
Honzík, Tomáš
The Phenotypic Spectrum of 47 Czech Patients with Single, Large-Scale Mitochondrial DNA Deletions
title The Phenotypic Spectrum of 47 Czech Patients with Single, Large-Scale Mitochondrial DNA Deletions
title_full The Phenotypic Spectrum of 47 Czech Patients with Single, Large-Scale Mitochondrial DNA Deletions
title_fullStr The Phenotypic Spectrum of 47 Czech Patients with Single, Large-Scale Mitochondrial DNA Deletions
title_full_unstemmed The Phenotypic Spectrum of 47 Czech Patients with Single, Large-Scale Mitochondrial DNA Deletions
title_short The Phenotypic Spectrum of 47 Czech Patients with Single, Large-Scale Mitochondrial DNA Deletions
title_sort phenotypic spectrum of 47 czech patients with single, large-scale mitochondrial dna deletions
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690373/
https://www.ncbi.nlm.nih.gov/pubmed/33105723
http://dx.doi.org/10.3390/brainsci10110766
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