A Common Trinucleotide Repeat Expansion within the Transcription Factor 4 (TCF4, E2-2) Gene Predicts Fuchs Corneal Dystrophy
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{"title"=>"A Common Trinucleotide Repeat Expansion within the Transcription Factor 4 (TCF4, E2-2) Gene Predicts Fuchs Corneal Dystrophy", "type"=>"journal", "authors"=>[{"first_name"=>"Eric D.", "last_name"=>"Wieben", "scopus_author_id"=>"7003825667"}, {"first_name"=>"Ross A.", "last_name"=>"Aleff", "scopus_author_id"=>"6508313742"}, {"first_name"=>"Nirubol", "last_name"=>"Tosakulwong", "scopus_author_id"=>"57200744981"}, {"first_name"=>"Malinda L.", "last_name"=>"Butz", "scopus_author_id"=>"8549404500"}, {"first_name"=>"W. Edward", "last_name"=>"Highsmith", "scopus_author_id"=>"7004210389"}, {"first_name"=>"Albert O.", "last_name"=>"Edwards", "scopus_author_id"=>"7403547867"}, {"first_name"=>"Keith H.", "last_name"=>"Baratz", "scopus_author_id"=>"6701320640"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-84869855274", "sgr"=>"84869855274", "pui"=>"366113249", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pmid"=>"23185296", "doi"=>"10.1371/journal.pone.0049083"}, "id"=>"a05dc350-f1ef-3516-b3ff-e47c43eae63e", "abstract"=>"Fuchs endothelial corneal dystrophy (FECD) is a common, familial disease of the corneal endothelium and is the leading indication for corneal transplantation. Variation in the transcription factor 4 (TCF4) gene has been identified as a major contributor to the disease. We tested for an association between an intronic TGC trinucleotide repeat in TCF4 and FECD by determining repeat length in 66 affected participants with severe FECD and 63 participants with normal corneas in a 3-stage discovery/replication/validation study. PCR primers flanking the TGC repeat were used to amplify leukocyte-derived genomic DNA. Repeat length was determined by direct sequencing, short tandem repeat (STR) assay and Southern blotting. Genomic Southern blots were used to evaluate samples for which only a single allele was identified by STR analysis. Compiling data for 3 arms of the study, a TGC repeat length >50 was present in 79% of FECD cases and in 3% of normal controls cases (p<0.001). Among cases, 52 of 66 (79%) subjects had >50 TGC repeats, 13 (20%) had <40 repeats and 1 (2%) had an intermediate repeat length. In comparison, only 2 of 63 (3%) unaffected control subjects had >50 repeats, 60 (95%) had <40 repeats and 1 (2%) had an intermediate repeat length. The repeat length was greater than 1000 in 4 FECD cases. The sensitivity and specificity of >50 TGC repeats identifying FECD in this patient cohort was 79% and 96%, respectively Expanded TGC repeat was more specific for FECD cases than the previously identified, highly associated, single nucleotide polymorphism, rs613872 (specificity = 79%). The TGC trinucleotide repeat expansion in TCF4 is strongly associated with FECD, and a repeat length >50 is highly specific for the disease This association suggests that trinucleotide expansion may play a pathogenic role in the majority of FECD cases and is a predictor of disease risk.", "link"=>"http://www.mendeley.com/research/common-trinucleotide-repeat-expansion-within-transcription-factor-4-tcf4-e22-gene-predicts-fuchs-cor", "reader_count"=>39, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Librarian"=>1, "Researcher"=>8, "Student > Doctoral Student"=>7, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>2, "Other"=>7, "Student > Master"=>3, "Student > Bachelor"=>2, "Professor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Librarian"=>1, "Researcher"=>8, "Student > Doctoral Student"=>7, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>2, "Other"=>7, "Student > Master"=>3, "Student > Bachelor"=>2, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>8, "Mathematics"=>1, "Medicine and Dentistry"=>15, "Agricultural and Biological Sciences"=>12, "Physics and Astronomy"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>15}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>12}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>8}, "Mathematics"=>{"Mathematics"=>1}, "Unspecified"=>{"Unspecified"=>2}}, "reader_count_by_country"=>{"Germany"=>1}, "group_count"=>2}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/537083"], "description"=>"<p>The trinucleotide repeat region is shown in red, and PCR primer sequences used for sizing the repeat region are underlined. This version of the sequence comes from the human reference sequence and contains 25 TGC repeats.</p>", "links"=>[], "tags"=>["trinucleotide", "intron", "chromosome"], "article_id"=>207562, "categories"=>["Molecular Biology", "Biological Sciences", "Genetics", "Medicine"], "users"=>["Eric D. Wieben", "Ross A. Aleff", "Nirubol Tosakulwong", "Malinda L. Butz", "W. Edward Highsmith", "Albert O. Edwards", "Keith H. Baratz"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0049083.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_DNA_sequence_surrounding_the_trinucleotide_repeat_in_the_intron_of_the_TCF4_gene_on_chromosome_18_/207562", "title"=>"DNA sequence surrounding the trinucleotide repeat in the intron of the <i>TCF4</i> gene on chromosome 18.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 19:46:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/537183"], "description"=>"<p>Sanger DNA sequencing of DNA samples of a normal control (A) and a FECD patient with two expanded alleles (B).</p>", "links"=>[], "tags"=>["dna", "sequencing", "samples", "fecd", "expanded", "alleles"], "article_id"=>207660, "categories"=>["Molecular Biology", "Biological Sciences", "Genetics", "Medicine"], "users"=>["Eric D. Wieben", "Ross A. Aleff", "Nirubol Tosakulwong", "Malinda L. Butz", "W. Edward Highsmith", "Albert O. Edwards", "Keith H. Baratz"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0049083.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Sanger_DNA_sequencing_of_DNA_samples_of_a_normal_control_A_and_a_FECD_patient_with_two_expanded_alleles_B_/207660", "title"=>"Sanger DNA sequencing of DNA samples of a normal control (A) and a FECD patient with two expanded alleles (B).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 19:46:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/537360"], "description"=>"<p>The bottom panel is the analysis of a FECD patient with 2 expanded alleles.</p>", "links"=>[], "tags"=>["pcr", "amplicons", "fecd", "patients"], "article_id"=>207849, "categories"=>["Molecular Biology", "Biological Sciences", "Genetics", "Medicine"], "users"=>["Eric D. Wieben", "Ross A. Aleff", "Nirubol Tosakulwong", "Malinda L. Butz", "W. Edward Highsmith", "Albert O. Edwards", "Keith H. Baratz"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0049083.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_STR_analysis_of_PCR_amplicons_of_3_normal_control_A_and_3_FECD_patients_B_/207849", "title"=>"STR analysis of PCR amplicons of 3 normal control (A) and 3 FECD patients (B).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 19:47:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/537531"], "description"=>"<p>Lanes 12 and 13 are laboratory control samples that have not been evaluated for FECD. Note that the samples in lanes 2, 3 and 6 are from FECD patients that do not have the repeat expansion. The samples in lanes 5, 9, and 10 are samples from FECD cases with repeat expansion over 1500 repeats. Lane L contains sizing standards.</p>", "links"=>[], "tags"=>["blot", "dna", "samples", "fecd", "patients"], "article_id"=>208016, "categories"=>["Molecular Biology", "Biological Sciences", "Genetics", "Medicine"], "users"=>["Eric D. Wieben", "Ross A. Aleff", "Nirubol Tosakulwong", "Malinda L. Butz", "W. Edward Highsmith", "Albert O. Edwards", "Keith H. Baratz"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0049083.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Genomic_Southern_Blot_of_DNA_samples_from_normal_control_lanes_1_4_7_and_8_and_FECD_patients_lanes_2_3_5_6_9_8211_11_/208016", "title"=>"Genomic Southern Blot of DNA samples from normal control (lanes 1, 4, 7 and 8) and FECD patients (lanes 2, 3, 5, 6, 9–11).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 19:48:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/537635"], "description"=>"<p>The length of the longest repeat in each sample is shown for both FECD patients (black bars) and normal control subjects (open bars). Note that 3 FECD patients had very long repeat expansions (more than 1500 repeats), as shown in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0049083#pone-0049083-g004\" target=\"_blank\">Figure 4</a>.</p>", "links"=>[], "tags"=>["histogram", "tgc", "longest", "allele", "129"], "article_id"=>208119, "categories"=>["Molecular Biology", "Biological Sciences", "Genetics", "Medicine"], "users"=>["Eric D. Wieben", "Ross A. Aleff", "Nirubol Tosakulwong", "Malinda L. Butz", "W. Edward Highsmith", "Albert O. Edwards", "Keith H. Baratz"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0049083.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Frequency_histogram_of_the_TGC_repeat_length_of_the_longest_allele_in_all_129_samples_/208119", "title"=>"Frequency histogram of the TGC repeat length of the longest allele in all 129 samples.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 19:49:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/537757"], "description"=>"*<p>p<0.001 for FECD cases vs. controls by Fisher's exact test.</p>", "links"=>[], "tags"=>["tgc", "tcf4", "fecd", "cases"], "article_id"=>208245, "categories"=>["Molecular Biology", "Biological Sciences", "Genetics", "Medicine"], "users"=>["Eric D. Wieben", "Ross A. Aleff", "Nirubol Tosakulwong", "Malinda L. Butz", "W. Edward Highsmith", "Albert O. Edwards", "Keith H. Baratz"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0049083.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_A_comparison_of_TGC_repeat_length_in_TCF4_between_FECD_cases_and_normal_controls_/208245", "title"=>"A comparison of TGC repeat length in TCF4 between FECD cases and normal controls.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-19 19:50:03"}

PMC Usage Stats | Further Information

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Relative Metric

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