ORPHA: 124; DO: 0111886;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 9q33.3 | ?Diamond-Blackfan anemia 19 | 618312 | Autosomal dominant | 3 | RPL35 | 618315 |
A number sign (#) is used with this entry because of evidence that Diamond-Blackfan anemia-19 (DBA19) is caused by heterozygous mutation in the RPL35 gene (618315) on chromosome 9q33. 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 mother and daughter (family NCI-138) with DBA19. The mother presented with anemia at 2 months of age and had spontaneous remission at age 18 years with no known relapse. Her daughter presented with steroid-responsive anemia at age 1 month. Bone marrow evaluation of both patients in infancy showed erythroid hypoplasia. The daughter developed ulcerative colitis at age 15 years and remained dependent on red cell transfusions while on treatment for colitis.
The transmission pattern of DBA19 in the family reported by Mirabello et al. (2017) was consistent with autosomal dominant inheritance.
In a mother and daughter with DBA19, Mirabello et al. (2017) identified a heterozygous missense mutation in the RPL35 gene (K77N; 618315.0001). Analysis of pre-rRNA processing in patient cells showed abnormal levels of several pre-rRNA subunits, indicating 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]