1ee54acdd54aec5a36de64a4d97da5ac pmc_33171734.pdf e6425fb2b551fc6431eb4f288f1c1bb9fb719463 pmc_33171734.pdf 3bd6ce15e1fc1875bc031c913fcb09e3118a2f7ce7a5b29fdc26e8072f133017 pmc_33171734.pdf Title: Preliminary Findings on CTG Expansion Determination in Different Tissues from Patients with Myotonic Dystrophy Type 1 Subject: Myotonic Dystrophy type 1 (DM1) is characterized by a high genetic and clinical variability. Determination of the genetic variability in DM1 might help to determine whether there is an association between CTG (Cytosine-Thymine-Guanine) expansion and the clinical manifestations of this condition. We studied the variability of the CTG expansion (progenitor, mode, and longest allele, respectively, and genetic instability) in three tissues (blood, muscle, and tissue) from eight patients with DM1. We also studied the association of genetic data with the patients’ clinical characteristics. Although genetic instability was confirmed in all the tissues that we studied, our results suggest that CTG expansion is larger in muscle and skin cells compared with peripheral blood leukocytes. While keeping in mind that more research is needed in larger cohorts, we have provided preliminary evidence suggesting that the estimated progenitor CTG size in muscle could be potentially used as an indicator of age of disease onset and muscle function impairment. Keywords: myotonic dystrophy type 1; somatic instability; CTG expansion; blood; muscle; skin Author: Alfonsina Ballester-Lopez, Emma Koehorst, Ian Linares-Pardo, Judit Núñez-Manchón, Miriam Almendrote, Giuseppe Lucente, Andrea Arbex, Carles Puente Alonso, Alejandro Lucia, Darren G. Monckton, Sarah A. Cumming, Guillem Pintos-Morell, Jaume Coll-Cantí, Alba Ramos-Fransi, Alicia Martínez-Piñeiro and Gisela Nogales-Gadea Creator: LaTeX with hyperref package Producer: pdfTeX-1.40.18 CreationDate: Wed Nov 11 10:26:54 2020 CET ModDate: Wed Nov 11 11:46:16 2020 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 8 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 968798 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- FXKWJE+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 QKQJSQ+Pxsy Type 1 Builtin yes yes no 15 0 SNDHFT+VnURWPalladioL Type 1 Custom yes yes no 19 0 ACGETK+URWPalladioL-Ital Type 1 Custom yes yes no 23 0 WGXNIR+URWPalladioL-Bold Type 1 Custom yes yes no 28 0 LZDGTK+Rpxb Type 1 Builtin yes yes no 32 0 KDFRHR+URWPalladioL-Roma Type 1 Custom yes yes no 36 0 FATHTC+Rpxr Type 1 Builtin yes yes no 40 0 CUAJJQ+Pxbsy Type 1 Builtin yes yes no 44 0 KONDUX+EuphemiaUCAS-Bold Type 1C WinAnsi yes yes no 52 0 HIZBRM+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 55 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 77 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 81 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 85 0 OVNEXW+EURM10 Type 1 Builtin yes yes no 92 0 ABCDEE+Palatino Linotype TrueType WinAnsi yes yes no 106 0 ABCDEE+Palatino Linotype,Italic TrueType WinAnsi yes yes no 110 0 ABCDEE+Palatino Linotype,Bold TrueType WinAnsi yes yes no 114 0 ABCDEE+Palatino Linotype CID TrueType Identity-H yes yes yes 118 0 Times New Roman TrueType WinAnsi no no no 125 0 ABCDEE+Palatino Linotype TrueType WinAnsi yes yes no 136 0 ABCDEE+Palatino Linotype,Italic TrueType WinAnsi yes yes no 140 0 ABCDEE+Palatino Linotype,Bold TrueType WinAnsi yes yes no 144 0 ABCDEE+Palatino Linotype CID TrueType Identity-H yes yes yes 148 0 Times New Roman TrueType WinAnsi no no no 155 0 VSHNAE+Rpcxr Type 1 Builtin yes yes no 168 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-06-01 02:30:12 CEST RepresentationInformation: pmc_33171734.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2020-11-30 03:47:26 CET Size: 968798 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 272 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Info: Title: Preliminary Findings on CTG Expansion Determination in Different Tissues from Patients with Myotonic Dystrophy Type 1 Author: Alfonsina Ballester-Lopez, Emma Koehorst, Ian Linares-Pardo, Judit Núñez-Manchón, Miriam Almendrote, Giuseppe Lucente, Andrea Arbex, Carles Puente Alonso, Alejandro Lucia, Darren G. Monckton, Sarah A. Cumming, Guillem Pintos-Morell, Jaume Coll-Cantí, Alba Ramos-Fransi, Alicia Martínez-Piñeiro and Gisela Nogales-Gadea Subject: Myotonic Dystrophy type 1 (DM1) is characterized by a high genetic and clinical variability. Determination of the genetic variability in DM1 might help to determine whether there is an association between CTG (Cytosine-Thymine-Guanine) expansion and the clinical manifestations of this condition. We studied the variability of the CTG expansion (progenitor, mode, and longest allele, respectively, and genetic instability) in three tissues (blood, muscle, and tissue) from eight patients with DM1. We also studied the association of genetic data with the patients’ clinical characteristics. Although genetic instability was confirmed in all the tissues that we studied, our results suggest that CTG expansion is larger in muscle and skin cells compared with peripheral blood leukocytes. While keeping in mind that more research is needed in larger cohorts, we have provided preliminary evidence suggesting that the estimated progenitor CTG size in muscle could be potentially used as an indicator of age of disease onset and muscle function impairment. 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