The Need for Establishing a Universal CTG Sizing Method in Myotonic Dystrophy Type 1
| Autor: | Gisela Nogales-Gadea, Ian Linares-Pardo, Emma Koehorst, Alba Ramos-Fransi, Jaume Coll-Cantí, Guillem Pintos-Morell, Jonathan J. Magaña, Andrea Arbex, Sarah A. Cumming, Alejandro Lucia, Alfonsina Ballester-Lopez, Darren G. Monckton, Alicia Martínez-Piñeiro, Miriam Almendrote, Giuseppe Lucente, Nadia M Murillo-Melo, Judit Núñez-Manchón |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Bioquímica musculoskeletal diseases congenital hereditary and neonatal diseases and abnormalities age of disease onset Disease onset lcsh:QH426-470 Long pcr Heat pulse CTG expansion size small pool-PCR Biology Genética humana Myotonic dystrophy Polymerase Chain Reaction Myotonin-Protein Kinase law.invention long PCR 03 medical and health sciences 0302 clinical medicine law Genetics medicine Humans Myotonic Dystrophy Clinical severity Genetic Testing Allele Age of Onset 3' Untranslated Regions myotonic dystrophy type 1 Genetics (clinical) Polymerase chain reaction Brief Report Reference Standards medicine.disease 3. Good health lcsh:Genetics 030104 developmental biology Sample size determination Trinucleotide Repeat Expansion 030217 neurology & neurosurgery |
| Zdroj: | Genes r-IGTP. Repositorio Institucional de Producción Científica del Instituto de Investigación Germans Trias i Pujol instname ABACUS. Repositorio de Producción Científica Universidad Europea (UEM) Genes, Vol 11, Iss 757, p 757 (2020) |
| ISSN: | 2073-4425 |
| Popis: | 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. © 2020 by the authors. Licensee MDPI, Basel, Switzerland. Sin financiación 4.096 JCR (2020) Q2, 65/175 Genetics & Heredity 1.337 SJR (2020) Q2, 99/340 Genetics No data IDR 2019 UEM |
| Databáze: | OpenAIRE |
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