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TBX5 mutations in non-Holt-Oram syndrome (HOS) malformed hearts.
Hum Mutat. 2004 Jul; 24(1):104.HM

Abstract

The T-box transcription factor Tbx5 is important in mammalian cardiac development. Mutations in the human TBX5 gene cause Holt-Oram syndrome (HOS), a disorder characterized by heart and upper limb deformities. To determine the role of TBX5 in non-HOS patients with complex cardiac malformations, we analyzed 68 explanted hearts from unrelated patients with various cardiac abnormalities including atrial (ASD), ventricular (VSD) and atrioventricular septal defects (AVSD). Direct sequencing detected nine mutations in diseased cardiac tissues of patients, eight of which are novel. Six mutations would affect amino acids in the T-domain, and one (c.236C>T, p.Ala79Val) is within the recently identified nuclear localization signal (NLS1) region. Further, mutations were found in patients with ASD and AVSD, but not with VSD; and mutations were absent in normal heart tissue of same patients, thus indicating somatic origin. Our results suggest a possible role of somatically occurring TBX5 mutations in congenital heart disease. We show for the first time TBX5 mutations in non-HOS associated cardiac malformations and we identified a novel missense mutation that would impact nuclear localization of TBX5.

Authors+Show Affiliations

Drug Research and Medical Biotechnology, Fraunhofer Institute of Toxicology and Experimental Medicine, D-30625 Hannover, Germany.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15221798

Citation

Reamon-Buettner, Stella Marie, and Juergen Borlak. "TBX5 Mutations in non-Holt-Oram Syndrome (HOS) Malformed Hearts." Human Mutation, vol. 24, no. 1, 2004, p. 104.
Reamon-Buettner SM, Borlak J. TBX5 mutations in non-Holt-Oram syndrome (HOS) malformed hearts. Hum Mutat. 2004;24(1):104.
Reamon-Buettner, S. M., & Borlak, J. (2004). TBX5 mutations in non-Holt-Oram syndrome (HOS) malformed hearts. Human Mutation, 24(1), 104.
Reamon-Buettner SM, Borlak J. TBX5 Mutations in non-Holt-Oram Syndrome (HOS) Malformed Hearts. Hum Mutat. 2004;24(1):104. PubMed PMID: 15221798.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - TBX5 mutations in non-Holt-Oram syndrome (HOS) malformed hearts. AU - Reamon-Buettner,Stella Marie, AU - Borlak,Juergen, PY - 2004/6/29/pubmed PY - 2004/11/9/medline PY - 2004/6/29/entrez SP - 104 EP - 104 JF - Human mutation JO - Hum. Mutat. VL - 24 IS - 1 N2 - The T-box transcription factor Tbx5 is important in mammalian cardiac development. Mutations in the human TBX5 gene cause Holt-Oram syndrome (HOS), a disorder characterized by heart and upper limb deformities. To determine the role of TBX5 in non-HOS patients with complex cardiac malformations, we analyzed 68 explanted hearts from unrelated patients with various cardiac abnormalities including atrial (ASD), ventricular (VSD) and atrioventricular septal defects (AVSD). Direct sequencing detected nine mutations in diseased cardiac tissues of patients, eight of which are novel. Six mutations would affect amino acids in the T-domain, and one (c.236C>T, p.Ala79Val) is within the recently identified nuclear localization signal (NLS1) region. Further, mutations were found in patients with ASD and AVSD, but not with VSD; and mutations were absent in normal heart tissue of same patients, thus indicating somatic origin. Our results suggest a possible role of somatically occurring TBX5 mutations in congenital heart disease. We show for the first time TBX5 mutations in non-HOS associated cardiac malformations and we identified a novel missense mutation that would impact nuclear localization of TBX5. SN - 1098-1004 UR - https://www.unboundmedicine.com/medline/citation/15221798/TBX5_mutations_in_non_Holt_Oram_syndrome__HOS__malformed_hearts_ L2 - https://doi.org/10.1002/humu.9255 DB - PRIME DP - Unbound Medicine ER -