ORPHA: 124; DO: 0111892;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 17p13.1 | ?Diamond-Blackfan anemia 11 | 614900 | Autosomal dominant | 3 | RPL26 | 603704 |
A number sign (#) is used with this entry because of evidence that Diamond-Blackfan anemia-11 (DBA11) is caused by heterozygous mutation in the RPL26 gene (603704) on chromosome 19q13. One such family has been reported.
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. (2012) studied a 3.5-year-old girl with Diamond-Blackfan anemia who was born with isolated cleft palate, absent external auditory meatus on the right and a narrowed meatus on the left, incomplete lower left eyelid, bicuspid aortic valve, and agenesis of the left kidney. In the right upper extremity, she had a single bone in the forearm, likely the ulna, and on the left, synostosis of a shortened radius and ulna; both thumbs were absent and she had 3 digits on each hand. She was anemic at birth, requiring transfusion twice during the perinatal period. By 7 weeks of age, she was again anemic and profoundly neutropenic; bone marrow examination showed cellularity of 40% with markedly decreased erythropoiesis. She had a good response to steroids and was maintained on a minimal dose with only occasional neutropenia and no further need for transfusions.
In a cohort of 96 families with Diamond-Blackfan anemia, the majority of whom had been included in previous reports (Gazda et al. (2006, 2008); Farrar et al., 2008; Doherty et al., 2010) and all of whom were negative for mutation in known DBA-associated genes, Gazda et al. (2012) sequenced 16 candidate ribosomal protein genes and identified a pathogenic mutation in 1 patient: a 3.5-year-old girl with anemia and multiple malformations who was heterozygous for a de novo 2-bp deletion in the RPL26 gene (603704.0001).
Doherty, L., Sheen, M. R., Vlachos, A., Choesmel, V., O'Donohue, M.-F., Clinton, C., Schneider, H. E., Sieff, C. A., Newburger, P. E., Ball, S. E., Niewiadomska, E., Matysiak, M., Glader, B., Arceci, R. J., Farrar, J. E., Atsidaftos, E., Lipton, J. M., Gleizes, P.-E., Gazda, H. T. Ribosomal protein genes RPS10 and RPS26 are commonly mutated in Diamond-Blackfan anemia. Am. J. Hum. Genet. 86: 222-228, 2010. Note: Erratum: Am. J. Hum. Genet 86: 655-656, 2010. [PubMed: 20116044] [Full Text: https://doi.org/10.1016/j.ajhg.2009.12.015]
Farrar, J. E., Nater, M., Caywood, E., McDevitt, M. A., Kowalski, J., Takemoto, C. M., Talbot, C. C., Jr., Meltzer, P., Esposito, D., Beggs, A. H., Schneider, H. E., Grabowska, A., and 9 others. Abnormalities of the large ribosomal subunit protein, Rpl35a, in Diamond-Blackfan anemia. Blood 112: 1582-1592, 2008. [PubMed: 18535205] [Full Text: https://doi.org/10.1182/blood-2008-02-140012]
Gazda, H. T., Grabowska, A., Merida-Long, L. B., Latawiec, E., Schneider, H. E., Lipton, J. M., Vlachos, A., Atsidaftos, E., Ball, S. E., Orfali, K. A., Niewiadomska, E., Da Costa, L., and 11 others. Ribosomal protein S24 gene is mutated in Diamond-Blackfan anemia. Am. J. Hum. Genet. 79: 1110-1118, 2006. [PubMed: 17186470] [Full Text: https://doi.org/10.1086/510020]
Gazda, H. T., Preti, M., Sheen, M. R., O'Donohue, M.-F., Vlachos, A., Davies, S. M., Kattamis, A., Doherty, L., Landowski, M., Buros, C., Ghazvinian, R., Sieff, C. A., Newburger, P. E., Niewiadomska, E., Matysiak, M., Glader, B., Atsidaftos, E., Lipton, J. M., Gleizes, P.-E., Beggs, A. H. Frameshift mutation of p53 regulator RPL26 is associated with multiple physical abnormalities and a specific pre-ribosomal RNA processing defect in Diamond-Blackfan anemia. Hum. Mutat. 33: 1037-1044, 2012. [PubMed: 22431104] [Full Text: https://doi.org/10.1002/humu.22081]
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]
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]