ORPHA: 124; DO: 0111881;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 2p25.3 | Diamond-Blackfan anemia 8 | 612563 | Autosomal dominant | 3 | RPS7 | 603658 |
A number sign (#) is used with this entry because Diamond-Blackfan anemia-8 (DBA8) is caused by heterozygous mutation in the gene encoding ribosomal protein S7 (RPS7; 603658) on chromosome 2p25.
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).
Gerrard et al. (2013) reported a 10-year-old Caucasian girl with Diamond-Blackfan anemia who was diagnosed at age 2 months. She had growth retardation, Cathie facies, and neutropenia. She underwent bone marrow transplantation from an unaffected sib.
Ichimura et al. (2017) studied a Japanese mother and daughter with DBA. The mother developed red cell aplasia due to erythroblastopenia in early infancy that was controlled by oral prednisolone. She was weaned off prednisolone for her pregnancy, and her daughter was born full-term. The daughter developed neonatal anemia, which was controlled by prednisolone, but did not require blood transfusions. Both affected individuals had elevated activity of the erythrocyte enzyme adenosine deaminase (ADA), and high normal to high levels of reduced glutathione (GSH). The patients exhibited no dysmorphic features other than short stature in the mother.
The transmission pattern of DBA8 in the patient reported by Gazda et al. (2008) was consistent with autosomal dominant inheritance.
Gazda et al. (2008) screened 196 probands with Diamond-Blackfan anemia for mutations in 25 genes encoding ribosomal proteins and identified a heterozygous splice site mutation in the RPS7 gene (603658.0001) in 1 proband, who had no associated malformations. The mutation was not found in his unaffected sister or at least 150 controls, and functional studies demonstrated defects in the maturation of ribosomal RNAs associated with mutation in the RPS7 gene.
Gerrard et al. (2013) identified a heterozygous splice site mutation in the RPS7 gene (603658.0001) in 1 of 19 patients with DBA who were screened for mutations in 80 ribosomal protein genes. Gerrard et al. (2013) stated that this was the same splice site mutation previously reported by Gazda et al. (2008).
By whole-exome sequencing in a Japanese mother and daughter with DBA, who were negative for mutation in genes associated with other inherited bone marrow failure syndromes, Ichimura et al. (2017) identified heterozygosity for a splice site mutation in the RPS7 gene (603658.0002).
Gazda, H. T., Sheen, M. R., Vlachos, A., Choesmel, V., O'Donohue, M.-F., Schneider, H., Darras, N., Hasman, C., Sieff, C. A., Newburger, P. E., Ball, S. E., Niewiadomska, E., and 9 others. Ribosomal protein L5 and L11 mutations are associated with cleft palate and abnormal thumbs in Diamond-Blackfan anemia patients. Am. J. Hum. Genet. 83: 769-780, 2008. [PubMed: 19061985] [Full Text: https://doi.org/10.1016/j.ajhg.2008.11.004]
Gerrard, G., Valganon, M., Foong, H. E., Kasperaviciute, D., Iskander, D., Game, L., Muller, M., Aitman, T. J., Roberts, I., de la Fuente, J., Foroni, L., Karadimitris, A. Target enrichment and high-throughput sequencing of 80 ribosomal protein genes to identify mutations associated with Diamond-Blackfan anaemia. Brit. J. Haemat. 162: 530-536, 2013. [PubMed: 23718193] [Full Text: https://doi.org/10.1111/bjh.12397]
Ichimura, T., Yoshida, K., Okuno, Y., Yujiri, T., Nagai, K., Nishi, M., Shiraishi, Y., Ueno, H., Toki, T., Chiba, K., Tanaka, H., Muramatsu, H., Hara, T., Kanno, H., Kojima, S., Miyano, S., Ito, E., Ogawa, S., Ohga, S. Diagnostic challenge of Diamond-Blackfan anemia in mothers and children by whole-exome sequencing. Int. J. Hemat. 105: 515-520, 2017. [PubMed: 27882484] [Full Text: https://doi.org/10.1007/s12185-016-2151-7]
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]