ORPHA: 124; DO: 0111890; MONDO: 0012924;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 15q25.2 | Diamond-Blackfan anemia 4 | 612527 | Autosomal dominant | 3 | RPS17 | 180472 |
A number sign (#) is used with this entry because of evidence that Diamond-Blackfan anemia-4 (DBA4) is caused by heterozygous mutation in the gene encoding ribosomal protein S17 (RPS17; 180472) on chromosome 15q25.
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 2 Caucasian sibs with Diamond-Blackfan anemia. One sib was diagnosed at birth, whereas the other sib was diagnosed at age 11 months. One had growth retardation and atrial septal defect; the other had hernia, neutropenia, and high erythrocyte adenosine deaminase (ADA; 608958) in cord blood. Both patients were treated successfully with steroids.
Cmejla et al. (2007) screened the RPS17 gene in 124 Czech patients with Diamond-Blackfan anemia, 6 of whom were already known to carry a heterozygous mutation in the RPS19 gene (603474), and identified a heterozygous mutation abolishing the translation initiation start codon of the RPS17 gene (180472.0001) in a 31-year-old male patient. The mutation was not found in his apparently healthy brother and parents or in 71 controls. In addition to the typical macrocytic anemia with increased activity of erythrocyte adenosine deaminase seen in DBA, the patient had short stature, facial dysmorphism, and a flat thenar eminence.
In a male patient who was diagnosed with DBA at 4 months of age and had no associated malformations, Gazda et al. (2008) identified heterozygosity for a 2-bp deletion in the RPS17 gene (180472.0002). The mutation was not found in his unaffected parents or sister, or in at least 150 controls.
Landowski et al. (2013) performed array CGH for copy number variation in 87 probands with Diamond-Blackfan anemia who were negative for mutation in 10 known DBA-associated ribosomal protein genes and identified 2 nearly identical large deletions involving exons 3, 4, and 5 of the RPS17 gene (180472.0003) in 2 male patients.
In 2 Caucasian sibs with Diamond-Blackfan anemia, Gerrard et al. (2013) identified a heterozygous nonsense mutation in the RPS17 gene (Y53X; 180472.0004). These patients were ascertained from a cohort of 19 patients with DBA who were screened for mutations in 80 ribosomal protein genes.
Cmejla, R., Cmejlova, J., Handrkova, H., Petrak, J., Pospisilova, D. Ribosomal protein S17 gene (RPS17) is mutated in Diamond-Blackfan anemia. Hum. Mutat. 28: 1178-1182, 2007. [PubMed: 17647292] [Full Text: https://doi.org/10.1002/humu.20608]
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]
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]