scholarly journals Fuchs' Endothelial Corneal Dystrophy and RNA Foci in Patients With Myotonic Dystrophy

2017 ◽  
Vol 58 (11) ◽  
pp. 4579 ◽  
Author(s):  
V. Vinod Mootha ◽  
Brock Hansen ◽  
Ziye Rong ◽  
Pradeep P. Mammen ◽  
Zhengyang Zhou ◽  
...  
Keyword(s):  
Myotonic Dystrophy ◽  
Corneal Dystrophy ◽  
Rna Foci

scholarly journals Duplex RNAs and ss-siRNAs Block RNA Foci Associated with Fuchs' Endothelial Corneal Dystrophy

2019 ◽  
Vol 29 (2) ◽  
pp. 73-81 ◽  
Author(s):  
Jiaxin Hu ◽  
Xiulong Shen ◽  
Frank Rigo ◽  
Thahza P. Prakash ◽  
V. Vinod Mootha ◽  
...  
Keyword(s):  
Corneal Dystrophy ◽  
Rna Foci

scholarly journals Fuchs Endothelial Corneal Dystrophy in Patients With Myotonic Dystrophy

Cornea ◽  
2014 ◽  
Vol 33 (1) ◽  
pp. 96-98 ◽  
Author(s):  
Devin Gattey ◽  
Angela Y. Zhu ◽  
Anna Stagner ◽  
Mark A. Terry ◽  
Albert S. Jun
Keyword(s):  
Myotonic Dystrophy ◽  
Corneal Dystrophy

Dual corneal involvement by endothelial and epithelial corneal dystrophies in Steinert’s disease: A case of triple dystrophy

2019 ◽  
pp. 112067211987237
Author(s):  
Amparo Gargallo-Benedicto ◽  
Vicente Tomás Pérez-Torregrosa ◽  
Rodrigo Clemente-Tomás ◽  
Antonio Miguel Duch-Samper
Keyword(s):  
Basement Membrane ◽  
Myotonic Dystrophy ◽  
Anterior Segment ◽  
Corneal Dystrophy ◽  
Specular Microscopy ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
Epithelial Basement Membrane ◽  
Epithelial Basement

Introduction: A case of dual corneal involvement due to Fuchs endothelial corneal dystrophy and epithelial basement membrane corneal dystrophy in a patient with Steinert’s myotonic dystrophy type 1 is described, and a literature review on the triple association is made. Case description: A 52-year-old male diagnosed with myotonic dystrophy type 1 presented due to progressive bilateral vision loss during the past year. A full ophthalmological evaluation was made, with biomicroscopy, funduscopy, anterior segment optical coherence tomography, and endothelial cell count using specular microscopy. Exploration revealed bilateral superior palpebral ptosis, visual acuity 0.5 in the right eye and 0.3 in the left eye, and with an intraocular pressure of 11 and 10 mmHg, respectively. Biomicroscopy revealed map-dot-fingerprint lesions characteristic of epithelial basement membrane corneal dystrophy in both eyes, as well as abundant endothelial guttae due to Fuchs endothelial corneal dystrophy (stage II) and bilateral nuclear and posterior subcapsular cataracts. Specular microscopy in turn showed cell loss and a destructured endothelial map. Finally, anterior segment optical coherence tomography revealed the accumulation of epithelial basement membrane and hyperreflective endothelial excrescences corresponding to guttae. Conclusion: The association of Fuchs endothelial corneal dystrophy with myotonic dystrophy has been described and explained by a common genetic basis in the expansion of a CTG trinucleotide repeat, though this is the first reported case of the triple association of Fuchs endothelial corneal dystrophy, epithelial basement membrane corneal dystrophy, and myotonic dystrophy type 1. New mutations or still unknown genetic alterations could possibly explain the triple association reported in our case.

scholarly journals BNANC Gapmers Revert Splicing and Reduce RNA Foci with Low Toxicity in Myotonic Dystrophy Cells

2017 ◽  
Vol 12 (10) ◽  
pp. 2503-2509 ◽  
Author(s):  
Kassie S. Manning ◽  
Ashish N. Rao ◽  
Miguel Castro ◽  
Thomas A. Cooper
Keyword(s):  
Myotonic Dystrophy ◽  
Rna Foci ◽  
Low Toxicity

scholarly journals Nuclear RNA Foci in the Heart in Myotonic Dystrophy

2005 ◽  
Vol 97 (11) ◽  
pp. 1152-1155 ◽  
Author(s):  
Ami Mankodi ◽  
Xiaoyan Lin ◽  
Burns C. Blaxall ◽  
Maurice S. Swanson ◽  
Charles A. Thornton
Keyword(s):  
Myotonic Dystrophy ◽  
Rna Foci ◽  
Nuclear Rna

scholarly journals TCF4Triplet Repeat Expansion and Nuclear RNA Foci in Fuchs' Endothelial Corneal Dystrophy

2015 ◽  
Vol 56 (3) ◽  
pp. 2003 ◽  
Author(s):  
V. Vinod Mootha ◽  
Imran Hussain ◽  
Khrishen Cunnusamy ◽  
Eric Graham ◽  
Xin Gong ◽  
...  
Keyword(s):  
Corneal Dystrophy ◽  
Repeat Expansion ◽  
Rna Foci ◽  
Nuclear Rna

scholarly journals Three-dimensional imaging in myotonic dystrophy type 1

2020 ◽  
Vol 6 (4) ◽  
pp. e484
Author(s):  
Alfonsina Ballester-Lopez ◽  
Judit Núñez-Manchón ◽  
Emma Koehorst ◽  
Ian Linares-Pardo ◽  
Miriam Almendrote ◽  
...  
Keyword(s):  
Myotonic Dystrophy ◽  
Disease Onset ◽  
Three Dimensional ◽  
Minor Role ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
Rna Foci ◽  
Cytoplasmic Rna ◽  
Ctg Expansion

ObjectiveWe aimed to determine whether 3D imaging reconstruction allows identifying molecular:clinical associations in myotonic dystrophy type 1 (DM1).MethodsWe 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.ResultsThree-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 (r = 0.876 [95% confidence interval 0.222–0.986]) as well as with the number of cytoplasmic RNA foci (r = 0.943 [0.559–0.994]). Although MBNL1 colocalized with RNA foci in all DM1 myoblast cell lines, colocalization only accounted for 1% of total MBNL1 expression, with the absence of DM1 alternative splicing patterns. The number of RNA foci was associated with DMPK expression (r = 0.967 [0.079–0.999]). On the other hand, the number of cytoplasmic RNA foci was correlated with the age at disease onset (r = −0.818 [−0.979 to 0.019]).ConclusionsCTG 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.

scholarly journals Fuchs' Endothelial Corneal Dystrophy in Patients With Myotonic Dystrophy, Type 1

2018 ◽  
Vol 59 (7) ◽  
pp. 3053 ◽  
Author(s):  
Nelson S. Winkler ◽  
Margherita Milone ◽  
Jennifer M. Martinez-Thompson ◽  
Harish Raja ◽  
Ross A. Aleff ◽  
...  
Keyword(s):  
Myotonic Dystrophy ◽  
Corneal Dystrophy ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type

scholarly journals Targeting Toxic Nuclear RNA Foci with CRISPR-Cas13 to Treat Myotonic Dystrophy

2019 ◽  
Author(s):  
Pornthida Poosala ◽  
Sean R. Lindley ◽  
Kelly M. Anderson ◽  
Douglas M. Anderson
Keyword(s):  
Myotonic Dystrophy ◽  
Rna Binding ◽  
Fluorescent Protein ◽  
Rna Binding Proteins ◽  
Live Cells ◽  
Nuclear Retention ◽  
Rna Foci ◽  
Nuclear Rna ◽  
Nuclear Foci ◽  
Dystrophia Myotonica Protein Kinase

Human monogenetic diseases can arise from the aberrant expansion of tandem nucleotide repeat sequences, which when transcribed into RNA, can misfold and aggregate into toxic nuclear foci1. Nuclear retention of repeat-containing RNAs can disrupt their normal expression and induce widespread splicing defects by sequestering essential RNA binding proteins. Among the most prevalent of these disorders is myotonic dystrophy type 1 (DM1), a disease occurring from the expression of a noncoding CTG repeat expansion in the 3’UTR of the human dystrophia myotonica protein kinase (DMPK) gene2,3. Here we show that RNA-binding CRISPR-Cas13, with a robust non-classical nuclear localization signal, can be efficiently targeted to toxic nuclear RNA foci for either visualization or cleavage, tools we named hilightR and eraseR, respectively. HilightR combines catalytically dead Cas13b (dCas13b) with a fluorescent protein to directly visualize CUG repeat RNA foci in the nucleus of live cells, allowing for quantification of foci number and observation of foci dynamics. EraseR utilizes the intrinsic endoribonuclease activity of Cas13b, targeted to nuclear CUG repeat RNA, to disrupt nuclear foci. These studies demonstrate the potential for targeting toxic nuclear RNA foci directly with CRISPR-Cas13 for either the identification or treatment of DM1. The efficient and sequence programmable nature of CRISPR-Cas13 systems will allow for rapid targeting and manipulation of other human nuclear RNA disorders, without the associated risks of genome editing.

scholarly journals Short Tandem Repeat Expansions and RNA-Mediated Pathogenesis in Myotonic Dystrophy

2019 ◽  
Vol 20 (13) ◽  
pp. 3365 ◽  
Author(s):  
Łukasz J. Sznajder ◽  
Maurice S. Swanson
Keyword(s):  
Myotonic Dystrophy ◽  
Tandem Repeat ◽  
Short Tandem Repeat ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Rna Foci ◽  
Repeat Expansions ◽  
Multivalent Interactions ◽  
Short Tandem

Short tandem repeat (STR) or microsatellite, expansions underlie more than 50 hereditary neurological, neuromuscular and other diseases, including myotonic dystrophy types 1 (DM1) and 2 (DM2). Current disease models for DM1 and DM2 propose a common pathomechanism, whereby the transcription of mutant DMPK (DM1) and CNBP (DM2) genes results in the synthesis of CUG and CCUG repeat expansion (CUGexp, CCUGexp) RNAs, respectively. These CUGexp and CCUGexp RNAs are toxic since they promote the assembly of ribonucleoprotein (RNP) complexes or RNA foci, leading to sequestration of Muscleblind-like (MBNL) proteins in the nucleus and global dysregulation of the processing, localization and stability of MBNL target RNAs. STR expansion RNAs also form phase-separated gel-like droplets both in vitro and in transiently transfected cells, implicating RNA-RNA multivalent interactions as drivers of RNA foci formation. Importantly, the nucleation and growth of these nuclear foci and transcript misprocessing are reversible processes and thus amenable to therapeutic intervention. In this review, we provide an overview of potential DM1 and DM2 pathomechanisms, followed by a discussion of MBNL functions in RNA processing and how multivalent interactions between expanded STR RNAs and RNA-binding proteins (RBPs) promote RNA foci assembly.

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