Mutations in cardiac T-box factor gene TBX20 are associated with diverse cardiac pathologies, including defects of septation and valvulogenesis and cardiomyopathy.

Mutations in cardiac T-box factor gene TBX20 are associated with diverse cardiac pathologies, including defects of septation and valvulogenesis and cardiomyopathy. Research Abstract Details 

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Mutations in cardiac T-box factor gene TBX20 are associated with diverse cardiac pathologies, including defects of septation and valvulogenesis and cardiomyopathy. Abstract Text:

Edwin P Kirk,Margaret Sunde,Mauro W Costa,Scott A Rankin,Orit Wolstein,M Leticia Castro,Tanya L Butler,Changbaig Hyun,Guanglan Guo,Robyn Otway,Joel P Mackay,Leigh B Waddell,Andrew D Cole,Christopher Hayward,Anne Keogh,Peter Macdonald,Lyn Griffiths,Diane Fatkin,Gary F Sholler,Aaron M Zorn,Michael P Feneley,David S Winlaw,Richard P Harvey,

The T-box family transcription factor gene TBX20 acts in a conserved regulatory network, guiding heart formation and patterning in diverse species. Mouse Tbx20 is expressed in cardiac progenitor cells, differentiating cardiomyocytes, and developing valvular tissue, and its deletion or RNA interference-mediated knockdown is catastrophic for heart development. TBX20 interacts physically, functionally, and genetically with other cardiac transcription factors, including NKX2-5, GATA4, and TBX5, mutations of which cause congenital heart disease (CHD). Here, we report nonsense (Q195X) and missense (I152M) germline mutations within the T-box DNA-binding domain of human TBX20 that were associated with a family history of CHD and a complex spectrum of developmental anomalies, including defects in septation, chamber growth, and valvulogenesis. Biophysical characterization of wild-type and mutant proteins indicated how the missense mutation disrupts the structure and function of the TBX20 T-box. Dilated cardiomyopathy was a feature of the TBX20 mutant phenotype in humans and mice, suggesting that mutations in developmental transcription factors can provide a sensitized template for adult-onset heart disease. Our findings are the first to link TBX20 mutations to human pathology. They provide insights into how mutation of different genes in an interactive regulatory circuit lead to diverse clinical phenotypes, with implications for diagnosis, genetic screening, and patient follow-up.

Mutations in cardiac T-box factor gene TBX20 are associated with diverse cardiac pathologies, including defects of septation and valvulogenesis and cardiomyopathy. Publishing Authors By Initials

EP Kirk,M Sunde,MW Costa,SA Rankin,O Wolstein,ML Castro,TL Butler,C Hyun,G Guo,R Otway,JP Mackay,LB Waddell,AD Cole,C Hayward,A Keogh,P Macdonald,L Griffiths,D Fatkin,GF Sholler,AM Zorn,MP Feneley,DS Winlaw,RP Harvey,

For similar proteins: dna-binding proteins: t-box domain proteins research abstracts see: proteins: dna-binding proteins: t-box domain proteins research

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Mutations in cardiac T-box factor gene TBX20 are associated with diverse cardiac pathologies, including defects of septation and valvulogenesis and cardiomyopathy. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: American journal of human genetics

VOLUME: 81

Page Numbers: 280-91

Journal Abbreviation: Am. J. Hum. Genet.

ISSN: 0002-9297

DAY: 15

MONTH: 06

YEAR: 2007

Mutations in cardiac T-box factor gene TBX20 are associated with diverse cardiac pathologies, including defects of septation and valvulogenesis and cardiomyopathy. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 370475

Mutations in cardiac T-box factor gene TBX20 are associated with diverse cardiac pathologies, including defects of septation and valvulogenesis and cardiomyopathy. Keywords Mesh Terms:

KEYWORDS: T-Box Domain Proteins

MESH TERMS: genetics

Chemical & Substance for Abstract: Mutations in cardiac T-box factor gene TBX20 are associated with diverse cardiac pathologies, including defects of septation and valvulogenesis and cardiomyopathy. Information

Substance Name: TBX20 protein, human

Registry Number: 0

Grant and Affiliation Information for Mutations in cardiac T-box factor gene TBX20 are associated with diverse cardiac pathologies, including defects of septation and valvulogenesis and cardiomyopathy.

AFFILIATION: Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, 2010, Australia.

Country: United States

AGENCY: United States NHLBI

GRANT: R01HL68885-01

ACRONYM: HL

MEDLINETA: Am J Hum Genet

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