User:Lanceweld

Tbx5 is a gene that is located on the long arm of chromosome 12.1 Tbx5 produces a protein called T-box 5 that acts as a transcription factor.2 The Tbx5 gene is involved with forelimb and heart development. This gene impacts the early development of the forelimb by triggering FGF-10 (Fibroblast Growth Factor 10).3 Tbx5 is involved with the development of the four chambers in the heart, the electrical conducting system, and the septum separating the right and left sides of the heart.4 A mutation in this gene can cause Holt-Oram syndrome or Amelia syndrome. Holt-Oram syndrome can cause several different defects. One effect of Holt-Oram syndrome is a hole in the septum.2 Another symptom of this syndrome is bone abnormalities in the fingers, wrists, or arms.5 An additional defect that Holt-Oram syndrome can cause is a conduction disease leading to abnormal heart rates and arrhythmias.1 Amelia syndrome is a condition where forelimb malformation occurs because FGF-10 is not triggered due to Tbx5 mutations.6 This condition can lead to the absence of one or both forelimbs.

1. Patel, C., Silcock, L., Mcmullan, D., Brueton, L., & Cox, H. (2012). TBX5 intragenic duplication: A family with an atypical Holt–Oram syndrome phenotype. European Journal of Human Genetics, 20(8), 863-869. doi:10.1038/ejhg.2012.16

2. Jhang, W. K., Lee, B. H., Kim, G., Lee, J., & Yoo, H. (2014). Clinical and molecular characterisation of Holt–Oram syndrome focusing on cardiac manifestations. Cardiology in the Young, 25(06), 1093-1098. doi:10.1017/s1047951114001656

3. Nishimoto, S., Wilde, S., Wood, S., & Logan, M. (2015). RA Acts in a Coherent Feed-Forward Mechanism with Tbx5 to Control Limb Bud Induction and Initiation. Cell Reports, 12(5), 879-891. doi:10.1016/j.celrep.2015.06.068

4. Boogerd, C., & Evans, S. (2016). Chamber-specific cardiac expression of Tbx5 and heart defects in Holt-Oram syndrome. Developmental Cell, 36(3), 242-244. doi:10.1016/j.devcel.2016.01.015

5. Pizard, A., Burgon, P. G., Paul, D. L., Bruneau, B. G., Seidman, C. E., & Seidman, J. G. (2005). Connexin 40, a Target of Transcription Factor Tbx5, Patterns Wrist, Digits, and Sternum. Molecular and Cellular Biology, 25(12), 5073-5083. doi:10.1128/mcb.25.12.5073-5083.2005

6. Pagon, R.A., Adam, M.P., Ardinger, H.H., Wallace, S.E., Amemiya, A., Bean, L.J.H., Bird, T.D., Dolan, C.R., Fong, C.T., Smith, R.J.H., Stephens, K. (2007). Tetra-Amelia Syndrome. GeneReviews. PMID 20301453.