American Journal of Medical Genetics March 2017 Congenital heart defects (CHD) affect approximately 1.35 million infants each year. New technologies have revealed more genetic causes for CHD; one gene of interest is TAB2 (Full name: TGF-beta activated kinase 1/MAP3K7 binding protein 2) which, as the study finds, causes structural valve abnormalities and defects involving the outflow tract of the heart.
This study describes the medical histories of 13 individuals with a 6q25.1 microdeletion, involving the TAB2 gene. Seven individuals of the study are members of one family (whom all have inherited this deletion); the other six are unrelated. One individual has a deletion that only includes the TAB2 gene. Comparing the features of this individual to the others in the study will help understand how important the TAB2 gene is to the symptoms of the microdeletion.
The individuals in the study share a number of distinct features: structural heart abnormalities, connective tissue abnormalities, dysmorphic facial features, poor fetal/infant growth, short stature, hypotonia (weak muscle tone), developmental delay, and intellectual disability. The severity of the issues differed between individuals, likely due to the variety of deletions sizes (and number of genes deleted) in each individual. The individual with the deletion that only included the TAB2 gene showed similar medical issues as those individuals with full deletions. This shows that the TAB2 gene is primarily responsible for these symptoms
TAB2 is expressed during development and aids in cardiac valve formation and the growth of the outflow tract of the heart. The structural heart deficits of the individuals in the study involve these areas of the heart:
outflow tract lesions (including bicuspid aortic valves), pulmonary valve dysplasia, atrial septal defects, ventricular septal defects, aortic dilation, and abnormalities of the mitral and tricuspid valves. TAB2 is also known to be involved in immune signaling and inflammatory responses. It signals to a number of other genes (specifically, MAP3K7) that are involved in myocardial issues and inflammatory responses during heart failure. Further research is necessary to understand the relationship between TAB2 and heart failure, but these findings reveal that TAB2 is involved in some cases.
The study concludes by restating its finding that TAB2 plays a key role in congenital heart defects, and further investigation of this gene could give rise to its role in heart failure. Cytogenomic microarray and similar tests should be considered in patients with these symptoms, as a mutation/deletion in the TAB2 gene may be the source of their issues. Since heart failure is a possibility later in life for those with this microdeletion, echocardiograms during adulthood should be considered a good preventive measure.