ORPHA: 124; DO: 0111896;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 19q13.33 | ?Diamond-Blackfan anemia 18 | 618310 | Autosomal dominant | 3 | RPL18 | 604179 |
A number sign (#) is used with this entry because of evidence that Diamond-Blackfan anemia-18 (DBA18) is caused by heterozygous mutation in the RPL18 gene (604179) on chromosome 19q13. One such family has been reported.
For a general phenotypic description and discussion of genetic heterogeneity of Diamond-Blackfan anemia, see DBA1 (105650).
Mirabello et al. (2017) reported a father and son (family NCI-172) with DBA18. The patients presented in the first year of life with steroid-responsive anemia associated with high levels of erythrocyte ADA, confirming the diagnosis. They also had neutropenia, but were able to mount appropriate responses to infection. Bone marrow aspirate and biopsy of both patients in infancy showed erythroid hypoplasia, maturation arrest of the erythroid series, granulocytopenia, and neutrophilic hypoplasia with lymphocytic infiltrate. Serum hemoglobin was low, and reticulocytes were increased in the father.
The transmission pattern of DBA18 in the family reported by Mirabello et al. (2017) was consistent with autosomal dominant inheritance.
In a father and son (family NCI-172) with DBA18, Mirabello et al. (2017) identified a heterozygous missense mutation in the RPL18 gene (L51S; 604179.0001). The mutation, which was found by whole-exome sequencing, was not found in the 1000 Genomes Project, Exome Variant Server, or ExAC databases. Analysis of pre-rRNA processing in patient cells showed an increase in the 36S subunit compared to controls, which indicated a defect in pre-rRNA processing. The patients were part of a cohort of 87 families with a similar disorder who underwent genetic analysis; mutations in known DBA-associated genes were excluded in the family.
Mirabello, L., Khincha, P. P., Ellis, S. R., Giri, N., Brodie, S., Chandrasekharappa, S. C., Donovan, F. X., Zhou, W., Hicks, B. D., Boland, J. F., Yeager, M., Jones, K., Zhu, B., Wang, M., Alter, B. P., Savage, S. A. Novel and known ribosomal causes of Diamond-Blackfan anaemia identified through comprehensive genomic characterisation. J. Med. Genet. 54: 417-425, 2017. [PubMed: 28280134] [Full Text: https://doi.org/10.1136/jmedgenet-2016-104346]