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...
Gespeichert in:
| Veröffentlicht in: | PloS one 2021-12, Vol.16 (12), p.e0260837 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 12 |
| container_start_page | e0260837 |
| container_title | PloS one |
| container_volume | 16 |
| creator | Wieben, Eric D Aleff, Ross A Rinkoski, Tommy A Baratz, Keith H Basu, Shubham Patel, Sanjay V Maguire, Leo J Fautsch, Michael P |
| 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 ( |
| doi_str_mv | 10.1371/journal.pone.0260837 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_2605598226</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A684621138</galeid><doaj_id>oai_doaj_org_article_070b8be78a04460c99836328afc01107</doaj_id><sourcerecordid>A684621138</sourcerecordid><originalsourceid>FETCH-LOGICAL-c692t-b71526df430cca49f257741c071c307f0dbfc7ef7c6b37854f3dfaeb391dd7c53</originalsourceid><addsrcrecordid>eNqNk9GK1DAUhoso7rr6BqIFQfBixqRpk_RGWAZHBxYWdPU2pGnSZmyTbpLqzgP43maczjoFBclFwsn3_wk_5yTJcwiWEBH4dmtHZ3i3HKyRS5BhQBF5kJzDEmULnAH08OR8ljzxfgtAgSjGj5MzlNOioCU-T36ubD9wp701qVXpzWqdp04OkodU3g3ceB0vOmma0KbapMI6I3mXSlPb0MpOj33KTR2J8ZsVuyD93mXgQUsTfPpDR9l6FK3_o4jqo0u988HZod09TR4p3nn5bNovki_r9zerj4ur6w-b1eXVQuAyC4uKwCLDtcoREILnpcoKQnIoAIECAaJAXSlBpCICV4jQIleoVlxWqIR1TUSBLpKXB9-hs55NCXoWwyuKkmYZjsTmQNSWb9ngdM_djlmu2e-CdQ3jLmjRSQYIqGglCeUgzzEQZUkRRhnlSgAIAYle76bXxqqXtYiRON7NTOc3Rressd8ZxYhSgqLBq8nA2dtR-vCPL09Uw-OvtFE2molee8EuMc1xBiGikVr-hYqrlr0WsYeUjvWZ4M1MEJkg70LDR-_Z5vOn_2evv87Z1ydsG_sgtN52Y4id5udgfgCFs947qe6Tg4DtR-CYBtuPAJtGIMpenKZ-Lzr2PPoF3bgDlw</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2605598226</pqid></control><display><type>article</type><title>Comparison of TCF4 repeat expansion length in corneal endothelium and leukocytes of patients with Fuchs endothelial corneal dystrophy</title><source>PubMed (Medline)</source><source>MEDLINE</source><source>Public Library of Science</source><source>DOAJ Directory of Open Access Journals</source><source>Free Full-Text Journals in Chemistry</source><source>EZB Electronic Journals Library</source><creator>Wieben, Eric D ; Aleff, Ross A ; Rinkoski, Tommy A ; Baratz, Keith H ; Basu, Shubham ; Patel, Sanjay V ; Maguire, Leo J ; Fautsch, Michael P</creator><creatorcontrib>Wieben, Eric D ; Aleff, Ross A ; Rinkoski, Tommy A ; Baratz, Keith H ; Basu, Shubham ; Patel, Sanjay V ; Maguire, Leo J ; Fautsch, Michael P</creatorcontrib><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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0260837</identifier><identifier>PMID: 34855896</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Aged ; Aged, 80 and over ; Analysis ; Biochemistry ; Biology and Life Sciences ; Blotting, Southern ; Child ; Cornea ; Corneal dystrophy ; Deoxyribonucleic acid ; DNA ; DNA - analysis ; DNA - genetics ; DNA sequencing ; Dystrophy ; Endothelium ; Endothelium, Corneal - metabolism ; Endothelium, Corneal - pathology ; Expansion ; Eye diseases ; Female ; Fuchs' Endothelial Dystrophy - epidemiology ; Fuchs' Endothelial Dystrophy - genetics ; Fuchs' Endothelial Dystrophy - pathology ; Gene sequencing ; Genetic Predisposition to Disease ; Genetic transcription ; Genotype ; Humans ; Leukocytes ; Leukocytes - metabolism ; Leukocytes - pathology ; Male ; Medicine and Health Sciences ; Middle Aged ; Molecular biology ; Nucleotide sequence ; Ophthalmology ; Peripheral blood ; Polymerase Chain Reaction ; Remakes & sequels ; Research and analysis methods ; Southern blotting ; Transcription Factor 4 - genetics ; Trinucleotide repeat diseases ; Trinucleotide Repeat Expansion ; Trinucleotide repeats</subject><ispartof>PloS one, 2021-12, Vol.16 (12), p.e0260837</ispartof><rights>COPYRIGHT 2021 Public Library of Science</rights><rights>2021 Wieben et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 Wieben et al 2021 Wieben et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-b71526df430cca49f257741c071c307f0dbfc7ef7c6b37854f3dfaeb391dd7c53</citedby><cites>FETCH-LOGICAL-c692t-b71526df430cca49f257741c071c307f0dbfc7ef7c6b37854f3dfaeb391dd7c53</cites><orcidid>0000-0002-9115-2485 ; 0000-0001-6694-1530</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8638873/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8638873/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34855896$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wieben, Eric D</creatorcontrib><creatorcontrib>Aleff, Ross A</creatorcontrib><creatorcontrib>Rinkoski, Tommy A</creatorcontrib><creatorcontrib>Baratz, Keith H</creatorcontrib><creatorcontrib>Basu, Shubham</creatorcontrib><creatorcontrib>Patel, Sanjay V</creatorcontrib><creatorcontrib>Maguire, Leo J</creatorcontrib><creatorcontrib>Fautsch, Michael P</creatorcontrib><title>Comparison of TCF4 repeat expansion length in corneal endothelium and leukocytes of patients with Fuchs endothelial corneal dystrophy</title><title>PloS one</title><addtitle>PLoS One</addtitle><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.</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Analysis</subject><subject>Biochemistry</subject><subject>Biology and Life Sciences</subject><subject>Blotting, Southern</subject><subject>Child</subject><subject>Cornea</subject><subject>Corneal dystrophy</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA - analysis</subject><subject>DNA - genetics</subject><subject>DNA sequencing</subject><subject>Dystrophy</subject><subject>Endothelium</subject><subject>Endothelium, Corneal - metabolism</subject><subject>Endothelium, Corneal - pathology</subject><subject>Expansion</subject><subject>Eye diseases</subject><subject>Female</subject><subject>Fuchs' Endothelial Dystrophy - epidemiology</subject><subject>Fuchs' Endothelial Dystrophy - genetics</subject><subject>Fuchs' Endothelial Dystrophy - pathology</subject><subject>Gene sequencing</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetic transcription</subject><subject>Genotype</subject><subject>Humans</subject><subject>Leukocytes</subject><subject>Leukocytes - metabolism</subject><subject>Leukocytes - pathology</subject><subject>Male</subject><subject>Medicine and Health Sciences</subject><subject>Middle Aged</subject><subject>Molecular biology</subject><subject>Nucleotide sequence</subject><subject>Ophthalmology</subject><subject>Peripheral blood</subject><subject>Polymerase Chain Reaction</subject><subject>Remakes & sequels</subject><subject>Research and analysis methods</subject><subject>Southern blotting</subject><subject>Transcription Factor 4 - genetics</subject><subject>Trinucleotide repeat diseases</subject><subject>Trinucleotide Repeat Expansion</subject><subject>Trinucleotide repeats</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk9GK1DAUhoso7rr6BqIFQfBixqRpk_RGWAZHBxYWdPU2pGnSZmyTbpLqzgP43maczjoFBclFwsn3_wk_5yTJcwiWEBH4dmtHZ3i3HKyRS5BhQBF5kJzDEmULnAH08OR8ljzxfgtAgSjGj5MzlNOioCU-T36ubD9wp701qVXpzWqdp04OkodU3g3ceB0vOmma0KbapMI6I3mXSlPb0MpOj33KTR2J8ZsVuyD93mXgQUsTfPpDR9l6FK3_o4jqo0u988HZod09TR4p3nn5bNovki_r9zerj4ur6w-b1eXVQuAyC4uKwCLDtcoREILnpcoKQnIoAIECAaJAXSlBpCICV4jQIleoVlxWqIR1TUSBLpKXB9-hs55NCXoWwyuKkmYZjsTmQNSWb9ngdM_djlmu2e-CdQ3jLmjRSQYIqGglCeUgzzEQZUkRRhnlSgAIAYle76bXxqqXtYiRON7NTOc3Rressd8ZxYhSgqLBq8nA2dtR-vCPL09Uw-OvtFE2molee8EuMc1xBiGikVr-hYqrlr0WsYeUjvWZ4M1MEJkg70LDR-_Z5vOn_2evv87Z1ydsG_sgtN52Y4id5udgfgCFs947qe6Tg4DtR-CYBtuPAJtGIMpenKZ-Lzr2PPoF3bgDlw</recordid><startdate>20211202</startdate><enddate>20211202</enddate><creator>Wieben, Eric D</creator><creator>Aleff, Ross A</creator><creator>Rinkoski, Tommy A</creator><creator>Baratz, Keith H</creator><creator>Basu, Shubham</creator><creator>Patel, Sanjay V</creator><creator>Maguire, Leo J</creator><creator>Fautsch, Michael P</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-9115-2485</orcidid><orcidid>https://orcid.org/0000-0001-6694-1530</orcidid></search><sort><creationdate>20211202</creationdate><title>Comparison of TCF4 repeat expansion length in corneal endothelium and leukocytes of patients with Fuchs endothelial corneal dystrophy</title><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></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-b71526df430cca49f257741c071c307f0dbfc7ef7c6b37854f3dfaeb391dd7c53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Analysis</topic><topic>Biochemistry</topic><topic>Biology and Life Sciences</topic><topic>Blotting, Southern</topic><topic>Child</topic><topic>Cornea</topic><topic>Corneal dystrophy</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA - analysis</topic><topic>DNA - genetics</topic><topic>DNA sequencing</topic><topic>Dystrophy</topic><topic>Endothelium</topic><topic>Endothelium, Corneal - metabolism</topic><topic>Endothelium, Corneal - pathology</topic><topic>Expansion</topic><topic>Eye diseases</topic><topic>Female</topic><topic>Fuchs' Endothelial Dystrophy - epidemiology</topic><topic>Fuchs' Endothelial Dystrophy - genetics</topic><topic>Fuchs' Endothelial Dystrophy - pathology</topic><topic>Gene sequencing</topic><topic>Genetic Predisposition to Disease</topic><topic>Genetic transcription</topic><topic>Genotype</topic><topic>Humans</topic><topic>Leukocytes</topic><topic>Leukocytes - metabolism</topic><topic>Leukocytes - pathology</topic><topic>Male</topic><topic>Medicine and Health Sciences</topic><topic>Middle Aged</topic><topic>Molecular biology</topic><topic>Nucleotide sequence</topic><topic>Ophthalmology</topic><topic>Peripheral blood</topic><topic>Polymerase Chain Reaction</topic><topic>Remakes & sequels</topic><topic>Research and analysis methods</topic><topic>Southern blotting</topic><topic>Transcription Factor 4 - genetics</topic><topic>Trinucleotide repeat diseases</topic><topic>Trinucleotide Repeat Expansion</topic><topic>Trinucleotide repeats</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wieben, Eric D</creatorcontrib><creatorcontrib>Aleff, Ross A</creatorcontrib><creatorcontrib>Rinkoski, Tommy A</creatorcontrib><creatorcontrib>Baratz, Keith H</creatorcontrib><creatorcontrib>Basu, Shubham</creatorcontrib><creatorcontrib>Patel, Sanjay V</creatorcontrib><creatorcontrib>Maguire, Leo J</creatorcontrib><creatorcontrib>Fautsch, Michael P</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Opposing Viewpoints In Context</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>ProQuest Nursing and Allied Health Journals</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>ProQuest Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Database (1962 - current)</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>https://resources.nclive.org/materials</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>Biological Sciences</collection><collection>Agriculture Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest advanced technologies & aerospace journals</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wieben, Eric D</au><au>Aleff, Ross A</au><au>Rinkoski, Tommy A</au><au>Baratz, Keith H</au><au>Basu, Shubham</au><au>Patel, Sanjay V</au><au>Maguire, Leo J</au><au>Fautsch, Michael P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Comparison of TCF4 repeat expansion length in corneal endothelium and leukocytes of patients with Fuchs endothelial corneal dystrophy</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2021-12-02</date><risdate>2021</risdate><volume>16</volume><issue>12</issue><spage>e0260837</spage><pages>e0260837-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>34855896</pmid><doi>10.1371/journal.pone.0260837</doi><tpages>e0260837</tpages><orcidid>https://orcid.org/0000-0002-9115-2485</orcidid><orcidid>https://orcid.org/0000-0001-6694-1530</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2021-12, Vol.16 (12), p.e0260837 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2605598226 |
| source | PubMed (Medline); MEDLINE; Public Library of Science; DOAJ Directory of Open Access Journals; Free Full-Text Journals in Chemistry; EZB Electronic Journals Library |
| subjects | Aged Aged, 80 and over Analysis Biochemistry Biology and Life Sciences Blotting, Southern Child Cornea Corneal dystrophy Deoxyribonucleic acid DNA DNA - analysis DNA - genetics DNA sequencing Dystrophy Endothelium Endothelium, Corneal - metabolism Endothelium, Corneal - pathology Expansion Eye diseases Female Fuchs' Endothelial Dystrophy - epidemiology Fuchs' Endothelial Dystrophy - genetics Fuchs' Endothelial Dystrophy - pathology Gene sequencing Genetic Predisposition to Disease Genetic transcription Genotype Humans Leukocytes Leukocytes - metabolism Leukocytes - pathology Male Medicine and Health Sciences Middle Aged Molecular biology Nucleotide sequence Ophthalmology Peripheral blood Polymerase Chain Reaction Remakes & sequels Research and analysis methods Southern blotting Transcription Factor 4 - genetics Trinucleotide repeat diseases Trinucleotide Repeat Expansion Trinucleotide repeats |
| title | Comparison of TCF4 repeat expansion length in corneal endothelium and leukocytes of patients with Fuchs endothelial corneal dystrophy |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-07T19%3A38%3A35IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Comparison%20of%20TCF4%20repeat%20expansion%20length%20in%20corneal%20endothelium%20and%20leukocytes%20of%20patients%20with%20Fuchs%20endothelial%20corneal%20dystrophy&rft.jtitle=PloS%20one&rft.au=Wieben,%20Eric%20D&rft.date=2021-12-02&rft.volume=16&rft.issue=12&rft.spage=e0260837&rft.pages=e0260837-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0260837&rft_dat=%3Cgale_plos_%3EA684621138%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2605598226&rft_id=info:pmid/34855896&rft_galeid=A684621138&rft_doaj_id=oai_doaj_org_article_070b8be78a04460c99836328afc01107&rfr_iscdi=true |