[8] The disease is characterized by genetic heterogeneity, affecting different ribosomal gene loci:[9] Exceptions to this paradigm have been demonstrated, such as with rare mutations of transcription factor GATA1.
[8] Given that ribosome function is essential for life, DBA patients carry loss-of-function alleles affecting only one copy.
Initial descriptions of DBA patients primarily concentrated on nonsense and missense mutations within ribosomal protein coding sequences.
[8] Recent studies have begun to characterize the molecular signatures associated with specific mutations that lead to aberrant splicing impacting ribosomal proteins such as RPL11.
Some previously undiagnosed relatives of DBA patients were found to carry mutations, and also had increased adenosine deaminase levels in their red blood cells, but had no other overt signs of disease.
[7] The genetic abnormalities underpinning the combination of DBA with Treacher Collins syndrome (TCS)/mandibulofacial dysostosis (MFD) phenotypes are heterogeneous, including RPS26 (the known DBA10 gene), TSR2 which encodes a direct binding partner of RPS26, and RPS28.
[21] The phenotype of DBA patients suggests a hematological stem cell defect specifically affecting the erythroid progenitor population.
[citation needed] Typically, a diagnosis of DBA is made through a blood count and a bone marrow biopsy.
A diagnosis of DBA is made on the basis of anemia, low reticulocyte (immature red blood cells) counts, and diminished erythroid precursors in bone marrow.
This option may be considered when patients become transfusion-dependent because frequent transfusions can lead to iron overloading and organ damage.
First noted by Hugh W. Josephs in 1936,[1][27] the condition is however named for the pediatricians Louis K. Diamond and Kenneth Blackfan, who described congenital hypoplastic anemia in 1938.