The need for establishing a universal CTG sizing method in myotonic dystrophy type 1

Ballester-Lopez, A. et al. (2020) The need for establishing a universal CTG sizing method in myotonic dystrophy type 1. Genes, 11(7), 757. (doi: 10.3390/genes11070757) (PMID:32645888)

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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.

Item Type:Articles
Additional Information:This research was supported by the following projects and institutions: PI15/01756, PI15/00558, PI18/00713, CD14/00032, CPII19/00021 and CM16/00016 (funded by ISCIII and co-financed by Fondos FEDER), AFM Telethon (Trampoline grant number #21108)), FI_B 01090 (Agaur), ID 100010434 and by SGR 1520 (GRC) Generalitat de Catalunya. LCF/BQ/IN18/11660019 (“La Caixa” Foundation co-funded by Marie Skłodowska-Curie grant agreement n°713673).
Glasgow Author(s) Enlighten ID:Monckton, Professor Darren and Cumming, Dr Sarah
Authors: Ballester-Lopez, A., Linares-Pardo, I., Koehorst, E., Núñez-Manchón, J., Pintos-Morell, G., Coll-Cantí, J., Almendrote, M., Lucente, G., Arbex, A., Magaña, J. J., Murillo-Melo, N. M., Lucia, A., Monckton, D., Cumming, S. A., Ramos-Fransi, A., Martínez-Piñeiro, A., and Nogales-Gadea, G.
College/School:College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
Journal Name:Genes
ISSN (Online):2073-4425
First Published:First published in Genes 11(7):757
Publisher Policy:Reproduced under a Creative Commons license

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