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The Need for Establishing a Universal CTG Sizing Method in Myotonic Dystrophy Type 1

The number of cytosine-thymine-guanine (CTG) repeats (‘CTG expansion size’) in the 3′untranslated region (UTR) region of the dystrophia myotonica-protein kinase (DMPK) gene is a hallmark of myotonic dystrophy type 1 (DM1), which has been related to age of disease onset and clinical severity. However...

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Autores principales: Ballester-Lopez, Alfonsina, Linares-Pardo, Ian, Koehorst, Emma, Núñez-Manchón, Judit, Pintos-Morell, Guillem, Coll-Cantí, Jaume, Almendrote, Miriam, Lucente, Giuseppe, Arbex, Andrea, Magaña, Jonathan J., Murillo-Melo, Nadia M., Lucia, Alejandro, Monckton, Darren G., Cumming, Sarah A., Ramos-Fransi, Alba, Martínez-Piñeiro, Alicia, Nogales-Gadea, Gisela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7397178/
https://www.ncbi.nlm.nih.gov/pubmed/32645888
http://dx.doi.org/10.3390/genes11070757
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author Ballester-Lopez, Alfonsina
Linares-Pardo, Ian
Koehorst, Emma
Núñez-Manchón, Judit
Pintos-Morell, Guillem
Coll-Cantí, Jaume
Almendrote, Miriam
Lucente, Giuseppe
Arbex, Andrea
Magaña, Jonathan J.
Murillo-Melo, Nadia M.
Lucia, Alejandro
Monckton, Darren G.
Cumming, Sarah A.
Ramos-Fransi, Alba
Martínez-Piñeiro, Alicia
Nogales-Gadea, Gisela
author_facet Ballester-Lopez, Alfonsina
Linares-Pardo, Ian
Koehorst, Emma
Núñez-Manchón, Judit
Pintos-Morell, Guillem
Coll-Cantí, Jaume
Almendrote, Miriam
Lucente, Giuseppe
Arbex, Andrea
Magaña, Jonathan J.
Murillo-Melo, Nadia M.
Lucia, Alejandro
Monckton, Darren G.
Cumming, Sarah A.
Ramos-Fransi, Alba
Martínez-Piñeiro, Alicia
Nogales-Gadea, Gisela
author_sort Ballester-Lopez, Alfonsina
collection PubMed
description The number of cytosine-thymine-guanine (CTG) repeats (‘CTG expansion size’) in the 3′untranslated region (UTR) region of the dystrophia myotonica-protein kinase (DMPK) gene is a hallmark of myotonic dystrophy type 1 (DM1), which has been related to age of disease onset and clinical severity. However, accurate determination of CTG expansion size is challenging due to its characteristic instability. We compared five different approaches (heat pulse extension polymerase chain reaction [PCR], long PCR-Southern blot [with three different primers sets—1, 2 and 3] and small pool [SP]-PCR) to estimate CTG expansion size in the progenitor allele as well as the most abundant CTG expansion size, in 15 patients with DM1. Our results indicated variability between the methods (although we found no overall differences between long PCR 1 and 2 and SP-PCR, respectively). While keeping in mind the limited sample size of our patient cohort, SP-PCR appeared as the most suitable technique, with an inverse significant correlation found between CTG expansion size of the progenitor allele, as determined by this method, and age of disease onset (r = −0.734, p = 0.016). Yet, in light of the variability of the results obtained with the different methods, we propose that an international agreement is needed to determine which is the most suitable method for assessing CTG expansion size in DM1.
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spelling pubmed-73971782020-08-16 The Need for Establishing a Universal CTG Sizing Method in Myotonic Dystrophy Type 1 Ballester-Lopez, Alfonsina Linares-Pardo, Ian Koehorst, Emma Núñez-Manchón, Judit Pintos-Morell, Guillem Coll-Cantí, Jaume Almendrote, Miriam Lucente, Giuseppe Arbex, Andrea Magaña, Jonathan J. Murillo-Melo, Nadia M. Lucia, Alejandro Monckton, Darren G. Cumming, Sarah A. Ramos-Fransi, Alba Martínez-Piñeiro, Alicia Nogales-Gadea, Gisela Genes (Basel) Brief Report The number of cytosine-thymine-guanine (CTG) repeats (‘CTG expansion size’) in the 3′untranslated region (UTR) region of the dystrophia myotonica-protein kinase (DMPK) gene is a hallmark of myotonic dystrophy type 1 (DM1), which has been related to age of disease onset and clinical severity. However, accurate determination of CTG expansion size is challenging due to its characteristic instability. We compared five different approaches (heat pulse extension polymerase chain reaction [PCR], long PCR-Southern blot [with three different primers sets—1, 2 and 3] and small pool [SP]-PCR) to estimate CTG expansion size in the progenitor allele as well as the most abundant CTG expansion size, in 15 patients with DM1. Our results indicated variability between the methods (although we found no overall differences between long PCR 1 and 2 and SP-PCR, respectively). While keeping in mind the limited sample size of our patient cohort, SP-PCR appeared as the most suitable technique, with an inverse significant correlation found between CTG expansion size of the progenitor allele, as determined by this method, and age of disease onset (r = −0.734, p = 0.016). Yet, in light of the variability of the results obtained with the different methods, we propose that an international agreement is needed to determine which is the most suitable method for assessing CTG expansion size in DM1. MDPI 2020-07-07 /pmc/articles/PMC7397178/ /pubmed/32645888 http://dx.doi.org/10.3390/genes11070757 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 Brief Report
Ballester-Lopez, Alfonsina
Linares-Pardo, Ian
Koehorst, Emma
Núñez-Manchón, Judit
Pintos-Morell, Guillem
Coll-Cantí, Jaume
Almendrote, Miriam
Lucente, Giuseppe
Arbex, Andrea
Magaña, Jonathan J.
Murillo-Melo, Nadia M.
Lucia, Alejandro
Monckton, Darren G.
Cumming, Sarah A.
Ramos-Fransi, Alba
Martínez-Piñeiro, Alicia
Nogales-Gadea, Gisela
The Need for Establishing a Universal CTG Sizing Method in Myotonic Dystrophy Type 1
title The Need for Establishing a Universal CTG Sizing Method in Myotonic Dystrophy Type 1
title_full The Need for Establishing a Universal CTG Sizing Method in Myotonic Dystrophy Type 1
title_fullStr The Need for Establishing a Universal CTG Sizing Method in Myotonic Dystrophy Type 1
title_full_unstemmed The Need for Establishing a Universal CTG Sizing Method in Myotonic Dystrophy Type 1
title_short The Need for Establishing a Universal CTG Sizing Method in Myotonic Dystrophy Type 1
title_sort need for establishing a universal ctg sizing method in myotonic dystrophy type 1
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7397178/
https://www.ncbi.nlm.nih.gov/pubmed/32645888
http://dx.doi.org/10.3390/genes11070757
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