Three-dimensional imaging in myotonic dystrophy type 1: Linking molecular alterations with disease phenotype.
Journal
Neurology. Genetics
ISSN: 2376-7839
Titre abrégé: Neurol Genet
Pays: United States
ID NLM: 101671068
Informations de publication
Date de publication:
Aug 2020
Aug 2020
Historique:
received:
21
02
2020
accepted:
05
06
2020
entrez:
18
8
2020
pubmed:
18
8
2020
medline:
18
8
2020
Statut:
epublish
Résumé
We aimed to determine whether 3D imaging reconstruction allows identifying molecular:clinical associations in myotonic dystrophy type 1 (DM1). We obtained myoblasts from 6 patients with DM1 and 6 controls. We measured cytosine-thymine-guanine (CTG) expansion and detected RNA foci and muscleblind like 1 (MBNL1) through 3D reconstruction. We studied dystrophia myotonica protein kinase (DMPK) expression and splicing alterations of MBNL1, insulin receptor, and sarcoplasmic reticulum Ca(2+)-ATPase 1. Three-dimensional analysis showed that RNA foci (nuclear and/or cytoplasmic) were present in 45%-100% of DM1-derived myoblasts we studied (range: 0-6 foci per cell). RNA foci represented <0.6% of the total myoblast nuclear volume. CTG expansion size was associated with the number of RNA foci per myoblast ( CTG expansion size modulates RNA foci number in myoblasts derived from patients with DM1. MBNL1 sequestration plays only a minor role in the pathobiology of the disease in these cells. Higher number of cytoplasmic RNA foci is related to an early onset of the disease, a finding that should be corroborated in future studies.
Identifiants
pubmed: 32802949
doi: 10.1212/NXG.0000000000000484
pii: NG2020013342
pmc: PMC7413607
doi:
Types de publication
Journal Article
Langues
eng
Pagination
e484Informations de copyright
Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
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