Most pedigrees suggest an autosomal dominant mode of inheritance with incomplete penetrance. Approximately 10–25% of DBA occurs with a family history of disease. About 25-50% of the causes of DBA have been tied to abnormal ribosomal protein genes. The disease is characterized by genetic heterogeneity, affecting different ribosomal gene loci: Exceptions to this paradigm have been demonstrated, such as with rare mutations of transcription factor GATA1 and advanced alternative splicing of a gene involved in iron metabolism, SLC49A1 (FLVCR1). DBA types name chromosome genotype phenotype protein disruption(cite)(cite) DBA1 19q13.2 RPS19 30S to 18S(cite) DBA2 8p23-p22 unknown DBA3 10q22-q23 RPS24 30S to 18S(cite) DBA4 15q RPS17 30S to 18S DBA5 3q29-qter RPL35A 32S to 5.8S/28S(cite) DBA6 1p22.1 RPL5 32S to 5.8S/28S DBA7 1p36.1-p35 RPL11 32S to 5.8S/28S DBA8 2p25 RPS7 30S to 18S DBA9 6p RPS10 30S to 18S DBA10 12q RPS26 30S to 18S DBA11 17p13 RPL26 30S to 18S DBA12 3p24 RPL15 45S to 32S DBA13 14q RPS29 "other" TSR2,RPS28, GATA1 SLC49A1 (FLVCR1) In 1997, a patient was identified who carried a rare balanced chromosomal translocation involving chromosome 19 and the X chromosome. This suggested that the affected gene might lie in one of the two regions that were disrupted by this cytogenetic anomaly. Linkage analysis in affected families also implicated this region in disease, and led to the cloning of the first DBA gene. About 20–25% of DBA cases are caused by mutations in the ribosome protein S19 (RPS19) gene on chromosome 19 at cytogenetic position 19q13.2. 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. A subsequent study of families with no evidence of RPS19 mutations determined that 18 of 38 families showed evidence for involvement of an unknown gene on chromosome 8 at 8p23.3-8p22. The precise genetic defect in these families has not yet been delineated. Malformations are seen more frequently with DBA6 RPL5 and DBA7 RPL11 mutations. 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. Molecular basis The phenotype of DBA patients suggests a hematological stem cell defect specifically affecting the erythroid progenitor population. Loss of ribosomal function might be predicted to affect translation and protein biosynthesis broadly and impact many tissues. However, DBA is characterized by dominant inheritance, and arises from partial loss of ribosomal function, so it is possible that erythroid progenitors are more sensitive to this decreased function, while most other tissues are less affected.
Diamond–Blackfan anemia
Fanconi anemia
Beta thalassemia
Delta-beta thalassemia
Congenital dyserythropoietic anemia type I
Congenital dyserythropoietic anemia type IV
Congenital dyserythropoietic anemia type II
Congenital dyserythropoietic anemia type III