Holt--Oram syndrome is a rare autosomal dominant condition resulting from a gene mutation on 12q24.1 (TBX5
) and causes anomalies in bony segment of the upper limbs and the cardiovascular system (1).
Dort ailede ise iliskili genlerdeki (SF3B4, SALL4, TBX5
, FANCA) mutasyonlar calisma oncesinde molekuler analizlerle belirlenmisti.
Briefly, Hand1 null (at e7.5-9.5) and Tbx5
null (at e9.5-10.5) mice are characterized by arrested cardiac development.
Direct reprogramming of fibroblasts into cardiomyocyte-like cells was first reported in 2010 using viral overexpression of three important cardiac developmental transcription factors (TFs), Gata4, Mef2c, and Tbx5
(GMT) in mouse cardiac and tail-tip fibroblasts .
Holt-Oram syndrome was previously excluded due to the lack of cardiac malformations and, more definitively, the lack of mutations within the TBX5
We also included potential upstream genes such as Csf1r , Gata4, Nkx2.5, and Tbx5
Rosengart, a team of researchers showed that administration of a cocktail made of transcription factors Gata4, Mef2c and Tbx5
(GMT) resulted in less scar tissue, or fibrosis, and up to a 50 percent increase in cardiac function in small animal models of the disease.
About 70% of the patients who meet the clinical diagnostic criteria have a mutation in TBX5
genes, which is associated with cardiac and skeletal development.
The protein NCBI IDs, NP_542377.1 (Tbx1), NP_005985.3 (Tbx2), NP_005987.3 (Tbx3), NP.001308049.1 (Tbx4), and NP.000183.2 (Tbx5
T-box transcription factor 5 (TBX5
) expression is high in RASFs and both H3K4me3 and histone acetylation are increased in the TBX5
promoter in RASFs .
Mutations in the gene TBX5
have been shown to cause both rare and more prevalent forms of congenital heart disease, yet the underlying mechanisms have remained unclear.