Mutations Predispose Individuals to Thoracic Aortic Aneurysms - Case Study Example

Independent measures were applied since different zebrafish were used in each condition of mat2aa MO injection. b. The control was a zebrafish with a normal phenotype with no injected MO, it had minimal pericardial effusion and no tail defects. After the injection, moderately affected showed large pericardial effusion and small eyes. Severe effects showed large pericardial effusion, small eyes, and severe tail curvature. d. From this data, it can be concluded that mat2aa MO injection in the zebrafish caused significant defects in embryonic development.

The developmental defects in the zebrafish were rescued by the wild-type MAT2A mRNA more significantly compared to the mutant MAT2A mRNAs encoding either the p.Gly344Ala variant or the p.Arg356Hs variant. 5. The overall findings of the paper indicate that MAT2A loss of function variants predispose individuals to FTAAD. In rescuing the knocked-out defects in the zebrafish, WT MAT2 was more effective compared to other mRNA variants that were previously studied. This was used to establish whether the human wildtype and p.

Gly344Ala and p.Arg356His mutant MAT2A mRNA rescued embryonic defects. 6. The main limitation in this research is that the disease progression is not known. The loss of function variants in MAT2A in FTAAD are predicted to lower cellular SAM levels which could lead to aortic disease through several pathways. It is probable that reduced SAM levels could decrease methylation activity or decrease glutathione activity that increases oxidative stress. It is possible that the pathology that leads to aortic disease due to loss of MAT IIα may overlap with mutations of Fibrillin-1(FBN1) a protein that is altered in individuals with Marfan syndrome. 7. Identification of the pathway by which decreased enzymatic activity of MAT IIα leads to thoracic aortic aneurysm.

Experiments that can help determine the pathway can be done by observing MAT IIα in zebrafish since they encode two MAT IIα paralogs (mat2aa and ma2ab) that have a high similarity to human MAT IIα.