GENETICS

The first DBA gene was identified in 1997 as RPS19, a gene which encodes a ribosomal protein (RP) on the small subunit of the ribosome. Approximately 20-25% of DBA patients have a mutation in this gene. Subsequently 11 more ribosomal protein genes have been discovered to be causative of DBA. These genes encode both small and large ribosomal proteins. Mutations as well as deletions have been identified in these genes and found in 65-70% of DBA patients. As of 2019, there are 24 DBA genes that have been identified. A specific bone marrow failure panel has been generated to test the genes listed below. 

24 Identified Genes

Genetic Testing 

Mutations in the GATA1 gene have been identified in a few families. This is the first non-ribosomal protein gene and opens up the search for more genes.

The 30-35% of patients without a known gene at this time will have a gene defect in genes yet to be determined

In the DBAR, some families report having more than one affected individual. With the discovery of the DBA genes, most of these families have been confirmed to have autosomal dominant inheritance (meaning gene transmission from a parent to a child). The GATA1 mutation is inherited as X-linked recessive, meaning that mothers without any known symptoms transmit the affected gene to their sons who are then affected with DBA. The DBAR investigators and their collaborators are looking for possible families with autosomal recessive inheritance, where each parent transmits one gene (carriers) and the patient needs 2 affected genes to have the disease.
 

Within affected families there is also great variability in the manifestations of DBA that is the degree of anemia, birth defects, treatment response, etc. For example, the parent may have mild anemia while the child is steroid or transfusion dependent, or the parent may be steroid responsive while the child does not respond to steroid and is transfusion dependent. Many different combinations within a family have been noted in the DBAR. In addition some affected members may have birth defects while others do not.