Cargando…

Comparison of TCF4 repeat expansion length in corneal endothelium and leukocytes of patients with Fuchs endothelial corneal dystrophy

Expansion of CTG trinucleotide repeats (TNR) in the transcription factor 4 (TCF4) gene is highly associated with Fuchs Endothelial Corneal Dystrophy (FECD). Due to limitations in the availability of DNA from diseased corneal endothelium, sizing of CTG repeats in FECD patients has typically been dete...

Descripción completa

Detalles Bibliográficos
Autores principales: Wieben, Eric D., Aleff, Ross A., Rinkoski, Tommy A., Baratz, Keith H., Basu, Shubham, Patel, Sanjay V., Maguire, Leo J., Fautsch, Michael P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8638873/
https://www.ncbi.nlm.nih.gov/pubmed/34855896
http://dx.doi.org/10.1371/journal.pone.0260837
_version_ 1784609029866127360
author Wieben, Eric D.
Aleff, Ross A.
Rinkoski, Tommy A.
Baratz, Keith H.
Basu, Shubham
Patel, Sanjay V.
Maguire, Leo J.
Fautsch, Michael P.
author_facet Wieben, Eric D.
Aleff, Ross A.
Rinkoski, Tommy A.
Baratz, Keith H.
Basu, Shubham
Patel, Sanjay V.
Maguire, Leo J.
Fautsch, Michael P.
author_sort Wieben, Eric D.
collection PubMed
description Expansion of CTG trinucleotide repeats (TNR) in the transcription factor 4 (TCF4) gene is highly associated with Fuchs Endothelial Corneal Dystrophy (FECD). Due to limitations in the availability of DNA from diseased corneal endothelium, sizing of CTG repeats in FECD patients has typically been determined using DNA samples isolated from peripheral blood leukocytes. However, it is non-feasible to extract enough DNA from surgically isolated FECD corneal endothelial tissue to determine repeat length based on current technology. To circumvent this issue, total RNA was isolated from FECD corneal endothelium and sequenced using long-read sequencing. Southern blotting of DNA samples isolated from primary cultures of corneal endothelium from these same affected individuals was also assessed. Both long read sequencing and Southern blot analysis showed significantly longer CTG TNR expansion (>1000 repeats) in the corneal endothelium from FECD patients than those characterized in leukocytes from the same individuals (<90 repeats). Our findings suggest that the TCF4 CTG repeat expansions in the FECD corneal endothelium are much longer than those found in leukocytes.
format Online
Article
Text
id pubmed-8638873
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-86388732021-12-03 Comparison of TCF4 repeat expansion length in corneal endothelium and leukocytes of patients with Fuchs endothelial corneal dystrophy Wieben, Eric D. Aleff, Ross A. Rinkoski, Tommy A. Baratz, Keith H. Basu, Shubham Patel, Sanjay V. Maguire, Leo J. Fautsch, Michael P. PLoS One Research Article Expansion of CTG trinucleotide repeats (TNR) in the transcription factor 4 (TCF4) gene is highly associated with Fuchs Endothelial Corneal Dystrophy (FECD). Due to limitations in the availability of DNA from diseased corneal endothelium, sizing of CTG repeats in FECD patients has typically been determined using DNA samples isolated from peripheral blood leukocytes. However, it is non-feasible to extract enough DNA from surgically isolated FECD corneal endothelial tissue to determine repeat length based on current technology. To circumvent this issue, total RNA was isolated from FECD corneal endothelium and sequenced using long-read sequencing. Southern blotting of DNA samples isolated from primary cultures of corneal endothelium from these same affected individuals was also assessed. Both long read sequencing and Southern blot analysis showed significantly longer CTG TNR expansion (>1000 repeats) in the corneal endothelium from FECD patients than those characterized in leukocytes from the same individuals (<90 repeats). Our findings suggest that the TCF4 CTG repeat expansions in the FECD corneal endothelium are much longer than those found in leukocytes. Public Library of Science 2021-12-02 /pmc/articles/PMC8638873/ /pubmed/34855896 http://dx.doi.org/10.1371/journal.pone.0260837 Text en © 2021 Wieben et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Wieben, Eric D.
Aleff, Ross A.
Rinkoski, Tommy A.
Baratz, Keith H.
Basu, Shubham
Patel, Sanjay V.
Maguire, Leo J.
Fautsch, Michael P.
Comparison of TCF4 repeat expansion length in corneal endothelium and leukocytes of patients with Fuchs endothelial corneal dystrophy
title Comparison of TCF4 repeat expansion length in corneal endothelium and leukocytes of patients with Fuchs endothelial corneal dystrophy
title_full Comparison of TCF4 repeat expansion length in corneal endothelium and leukocytes of patients with Fuchs endothelial corneal dystrophy
title_fullStr Comparison of TCF4 repeat expansion length in corneal endothelium and leukocytes of patients with Fuchs endothelial corneal dystrophy
title_full_unstemmed Comparison of TCF4 repeat expansion length in corneal endothelium and leukocytes of patients with Fuchs endothelial corneal dystrophy
title_short Comparison of TCF4 repeat expansion length in corneal endothelium and leukocytes of patients with Fuchs endothelial corneal dystrophy
title_sort comparison of tcf4 repeat expansion length in corneal endothelium and leukocytes of patients with fuchs endothelial corneal dystrophy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8638873/
https://www.ncbi.nlm.nih.gov/pubmed/34855896
http://dx.doi.org/10.1371/journal.pone.0260837
work_keys_str_mv AT wiebenericd comparisonoftcf4repeatexpansionlengthincornealendotheliumandleukocytesofpatientswithfuchsendothelialcornealdystrophy
AT aleffrossa comparisonoftcf4repeatexpansionlengthincornealendotheliumandleukocytesofpatientswithfuchsendothelialcornealdystrophy
AT rinkoskitommya comparisonoftcf4repeatexpansionlengthincornealendotheliumandleukocytesofpatientswithfuchsendothelialcornealdystrophy
AT baratzkeithh comparisonoftcf4repeatexpansionlengthincornealendotheliumandleukocytesofpatientswithfuchsendothelialcornealdystrophy
AT basushubham comparisonoftcf4repeatexpansionlengthincornealendotheliumandleukocytesofpatientswithfuchsendothelialcornealdystrophy
AT patelsanjayv comparisonoftcf4repeatexpansionlengthincornealendotheliumandleukocytesofpatientswithfuchsendothelialcornealdystrophy
AT maguireleoj comparisonoftcf4repeatexpansionlengthincornealendotheliumandleukocytesofpatientswithfuchsendothelialcornealdystrophy
AT fautschmichaelp comparisonoftcf4repeatexpansionlengthincornealendotheliumandleukocytesofpatientswithfuchsendothelialcornealdystrophy