ORPHA: 124; DO: 0111889;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 14q21.3 | Diamond-Blackfan anemia 13 | 615909 | Autosomal dominant | 3 | RPS29 | 603633 |
A number sign (#) is used with this entry because of evidence that Diamond-Blackfan anemia-13 (DBA13) is caused by heterozygous mutation in the RPS29 gene (603633) on chromosome 14q.
For a discussion of genetic heterogeneity of Diamond-Blackfan anemia, see DBA1 (105650).
Mirabello et al. (2014) reported a 2-generation family in which 5 individuals developed Diamond-Blackfan anemia between 3 months and 9 years of age. The severity was variable: 4 patients responded to steroids and were in remission as adults, whereas the disorder was refractory to steroids in 1 patient, who underwent bone marrow transplant. None of the patients had dysmorphic features, and 1 patient who was a smoker developed lung cancer at age 56. Laboratory studies showed increased erythrocyte adenosine deaminase in most patients and in 1 asymptomatic carrier. A 25-year-old man in an unrelated family presented with DBA at age 2 years. The disorder was responsive to steroid treatment, and he was in remission from age 4 years. He did not have dysmorphic features. An asymptomatic half-sib had increased erythrocyte adenosine deaminase. Both families had several members with cancer.
The transmission pattern of DBA13 in the families reported by Mirabello et al. (2014) was consistent with autosomal dominant inheritance and incomplete penetrance.
In affected members of 2 unrelated families with Diamond-Blackfan anemia, Mirabello et al. (2014) identified heterozygous missense mutations in the RPS29 gene (603633.0001 and 603633.0002). The mutations, which were found by whole-exome sequencing, segregated with the disorder in the families; however, both families showed evidence of incomplete penetrance. Functional studies showed that the mutations caused haploinsufficiency of RPS29.
Mirabello, L., Macari, E. R., Jessop, L., Ellis, S. R., Myers, T., Giri, N., Taylor, A. M., McGrath, K. E., Humphries, J. M., Ballew, B. J., Yeager, M., Boland, J. F., He, J., Hicks, B. D., Burdett, L., Alter, B. P., Zon, L., Savage, S. A. Whole-exome sequencing and functional studies identify RPS29 as a novel gene mutated in multicase Diamond-Blackfan anemia families. Blood 124: 24-32, 2014. [PubMed: 24829207] [Full Text: https://doi.org/10.1182/blood-2013-11-540278]