Startseite TBX20 loss-of-function mutation associated with familial dilated cardiomyopathy
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TBX20 loss-of-function mutation associated with familial dilated cardiomyopathy

  • Cui-Mei Zhao , Bing-Sun , Hao-Ming Song , Juan Wang , Wen-Jun Xu , Jin-Fa Jiang , Xing-Biao Qiu , Fang Yuan , Jia-Hong Xu EMAIL logo und Yi-Qing Yang EMAIL logo
Veröffentlicht/Copyright: 23. Juni 2015
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Clinical Chemistry and Laboratory Medicine (CCLM)
Aus der Zeitschrift Clinical Chemistry and Laboratory Medicine (CCLM) Band 54 Heft 2

Abstract

Background: Dilated cardiomyopathy (DCM) is a major cause of congestive heart failure, sudden cardiac death and cardiac transplantation. Aggregating evidence highlights the genetic origin of DCM. However, DCM is a genetically heterogeneous disorder, and the genetic components underlying DCM in most cases remain unknown.

Methods: The coding regions and splicing junction sites of the TBX20 gene were sequenced in 120 unrelated patients with idiopathic DCM. The available close relatives of the index patient carrying an identified mutation and 300 unrelated ethnically matched healthy individuals used as controls were genotyped for TBX20. The functional characteristics of the mutant TBX20 were assayed in contrast to its wild-type counterpart by using a dual-luciferase reporter assay system.

Results: A novel heterozygous TBX20 mutation, p.F256I, was identified in a family with DCM transmitted in an autosomal dominant fashion, which co-segregated with DCM in the family with complete penetrance. The missense mutation was absent in 600 control chromosomes and the altered amino acid was completely conserved evolutionarily among various species. Functional assays revealed that the mutant TBX20 had significantly diminished transcriptional activity. Furthermore, the mutation markedly reduced the synergistic activation of TBX20 with NKX2-5 or GATA4.

Conclusions: This study links TBX20 loss-of-function mutation to idiopathic DCM in humans for the first time, providing novel insight into the molecular mechanism underpinning DCM.

Keywords: dilated cardiomyopathy; genetics; reporter gene assay; TBX20; transcription factor
Corresponding authors: Dr. Jia-Hong Xu, Department of Cardiology, Tongji Hospital, Tongji University School of Medicine, 389 Xincun Road, Shanghai 200065, P. R. China, Phone: +86 21 56051080, Fax: +86 21 66371663, E-mail: ; Dr. Yi-Qing Yang, Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 West Huaihai Road, Shanghai 200030, P. R. China, Phone: +86 21 62821990, Fax: +86 21 62821105, E-mail:
aCui-Mei Zhao, Bing-Sun and Hao-Ming Song contributed equally to this work.

Acknowledgments

We are grateful to the subjects for their participation in the study. This work was supported by grants from the National Natural Science Fund of China (81270161), the key program for Basic Research of Shanghai, China (14JC1405500), and the Natural Science Fund of Shanghai, China (14ZR1438000).

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Supplemental Material:

The online version of this article (DOI: 10.1515/cclm-2015-0328) offers supplementary material, available to authorized users.

Received: 2015-4-8
Accepted: 2015-6-1
Published Online: 2015-6-23
Published in Print: 2016-2-1

©2016 by De Gruyter

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https://doi.org/10.1515/cclm-2015-0328
Schlagwörter für diesen Artikel
dilated cardiomyopathy; genetics; reporter gene assay; TBX20; transcription factor

Artikel in diesem Heft

  1. Frontmatter
  2. Editorial
  3. Total error vs. measurement uncertainty: the match continues
  4. Review
  5. Application of fatty acid and lipid measurements in neuropsychiatry
  6. Mini Review
  7. The Janus faces of acquired angioedema: C1-inhibitor deficiency, lymphoproliferation and autoimmunity
  8. Opinion Papers
  9. How to report results of prothrombin and activated partial thromboplastin times
  10. Useful measures and models for analytical quality management in medical laboratories
  11. Total error vs. measurement uncertainty: revolution or evolution?
  12. Genetics and Molecular Diagnostics
  13. Rapid detection of Mmalton α1-antitrypsin deficiency allele by real-time PCR and melting curves in whole blood, serum and dried blood spot samples
  14. General Clinical Chemistry and Laboratory Medicine
  15. Diagnostic and clinical significance of Crohn’s disease-specific pancreatic anti-GP2 and anti-CUZD1 antibodies
  16. Immunoassays for the detection of IgA antibodies to tissue transglutaminase: significance of multiples of the upper limit of normal and inter-assay correlations
  17. Effects of biobanking conditions on six antibiotic substances in human serum assessed by a novel evaluation protocol
  18. Haematology and Coagulation
  19. Measurement of dabigatran, rivaroxaban and apixaban in samples of plasma, serum and urine, under real life conditions. An international study
  20. Reference Values and Biological Variations
  21. Upper reference limits for cerebrospinal fluid total protein and albumin quotient based on a large cohort of control patients: implications for increased clinical specificity
  22. Reference intervals for bone turnover markers in Spanish premenopausal women
  23. Cancer Diagnostics
  24. Citrulline as a biomarker of gastrointestinal toxicity in patients with rectal carcinoma treated with chemoradiation
  25. mRNA overexpression of kallikrein-related peptidase 14 (KLK14) is an independent predictor of poor overall survival in chronic lymphocytic leukemia patients
  26. Cardiovascular Diseases
  27. TBX20 loss-of-function mutation associated with familial dilated cardiomyopathy
  28. Cardiac troponin I release after a basketball match in elite, amateur and junior players
  29. The role of timely measurement of galectin-3, NT-proBNP, cystatin C and hsTnT in predicting prognosis and heart function after heart transplantation
  30. Infectious Diseases
  31. Neutrophil CD64 combined with PCT, CRP and WBC improves the sensitivity for the early diagnosis of neonatal sepsis
  32. A comparison of three commercial platforms for urinary NGAL in critically ill adults
  33. Diabetes
  34. Liquid citrate acidification introduces significant glucose bias and leads to misclassification of patients with diabetes
  35. Letter to the Editors
  36. A rare and unstable hemoglobin variant, Hb M Dothan β 25/26 (-GTG), detected by the anomalous cytogram on Sysmex XE-2100
  37. Hb Hope [β136Gly→Asp] and Hb Grady [α119_120insGluPheThr] compound heterozygosity in a Mauritanian patient
  38. Falsely elevated ferritin in patients with a high concentration of rheumatoid factor
  39. Susceptibility of commonly used ferritin assays to the classic hook effect
  40. Comparison of the Elecsys calcitonin assay with the Immulite 1000 assay. Describing one case with heterophilic antibody interference
  41. Performance evaluation of low platelet count and platelet clumps detection on Mindray BC-6800 hematology analyzer
  42. Fetal sex discordance between sequencing-based and real-time PCR non-invasive prenatal test due to a vanishing twin
  43. Total HIV-1 DNA detection and quantification in peripheral blood by COBAS®AmpliPrep/COBAS® TaqMan® HIV-1 Test, v2.0
  44. A replacement for the testosterone “sex gap”
  45. Added value of indirect immunofluorescence intensity of automated antinuclear antibody testing in a secondary hospital setting
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