ORPHA: 124; DO: 0111885;
Cytogenetic location: 8p23.3-p22 Genomic coordinates (GRCh38): 8:1-19,200,000
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 8p23.3-p22 | Diamond-Blackfan anemia 2 | 606129 | 2 |
Diamond-Blackfan anemia (DBA) is an inherited red blood cell aplasia that usually presents in the first year of life. The main features are normochromic macrocytic anemia, reticulocytopenia, and nearly absent erythroid progenitors in the bone marrow. Patients show growth retardation, and approximately 30 to 50% have craniofacial, upper limb, heart, and urinary system congenital malformations. The majority of patients have increased mean corpuscular volume, elevated erythrocyte adenosine deaminase activity, and persistence of hemoglobin F. However, some DBA patients do not exhibit these findings, and even in the same family, symptoms can vary between affected family members (summary by Landowski et al., 2013).
For a discussion of genetic heterogeneity of Diamond-Blackfan anemia, see DBA1 (105650).
Gazda et al. (2001) analyzed 14 multiplex DBA families, 9 of which had 19q13.2 haplotypes inconsistent with 19q linkage. A genomewide search for a linked locus suggested the presence of a DBA locus on 8p. The authors ascertained another 24 DBA families and analyzed all 38 families with additional polymorphic markers on 8p. In total, 18 of 38 families were consistent with linkage to 8p with a maximum lod score with heterogeneity of 3.55 at D8S277 assuming 90% penetrance. The results indicated the existence of a second DBA locus on 8p23.3-p22, most likely within an 8.1-cM interval flanked by D8S518 and D8S1825. Seven families were inconsistent with linkage to either 8p or 19q, thus suggesting further genetic heterogeneity.
Gazda, H., Lipton, J. M., Willig, T.-N., Ball, S., Niemeyer, C. M., Tchernia, G., Mohandas, N., Daly, M. J., Ploszynska, A., Orfali, K. A., Vlachos, A., Glader, B. E., Rokicka-Milewska, R., Ohara, A., Baker, D., Pospisilova, D., Webber, A., Viskochil, D. H., Nathan, D. G., Beggs, A. H., Sieff, C. A. Evidence for linkage of familial Diamond-Blackfan anemia to chromosome 8p23.3-p22 and for non-19q non-8p disease. Blood 97: 2145-2150, 2001. [PubMed: 11264183] [Full Text: https://doi.org/10.1182/blood.v97.7.2145]
Landowski, M., O'Donohue, M.-F., Buros, C., Ghazvinian, R., Montel-Lehry, N., Vlachos, A., Sieff, C. A., Newburger, P. E., Niewiadomska, E., Matysiak, M., Glader, B., Atsidaftos, E., Lipton, J. M., Beggs, A. H., Gleizes, P.-E., Gazda, H. T. Novel deletion of RPL15 identified by array-comparative genomic hybridization in Diamond-Blackfan anemia. Hum. Genet. 132: 1265-1274, 2013. [PubMed: 23812780] [Full Text: https://doi.org/10.1007/s00439-013-1326-z]