ORPHA: 124; DO: 0111891;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 16p12.3 | ?Diamond-Blackfan anemia 20 | 618313 | Autosomal dominant | 3 | RPS15A | 603674 |
A number sign (#) is used with this entry because of evidence that Diamond-Blackfan anemia-20 (DBA20) is caused by heterozygous mutation in the RPS15A gene (603674) on chromosome 16p12. One such family has been reported.
For a general phenotypic description and discussion of genetic heterogeneity of Diamond-Blackfan anemia, see DBA1 (105650).
Ikeda et al. (2017) reported a mother and 2 daughters with DBA20. The proband, who was the youngest daughter, was the most severely affected. She presented at birth with total anomalous pulmonary venous connection and acetabular dysplasia, and was diagnosed with anemia at age 3 months. Bone marrow aspiration showed severe selective erythroid hypoplasia, but otherwise normal cellularity. She developed macrocytosis at age 14. The mother and sister presented with anemia during childhood, but had no additional physical abnormalities. All 3 patients initially responded to corticosteroid treatment and later became steroid-independent.
The transmission pattern of DBA20 in the family reported by Ikeda et al. (2017) was consistent with autosomal dominant inheritance.
In a mother and 2 daughters with DBA20, Ikeda et al. (2017) identified a heterozygous splicing mutation in the RPS15A gene (603674.0001) that was demonstrated to result in a loss of function and haploinsufficiency. The mutation, which was found by whole-exome sequencing and confirmed by direct sequencing, segregated with the disorder in the family. It was not found in the ExAC database. Expression of the mutation in human erythroid K562 cells showed that it suppressed cell proliferation and caused abnormal levels of several pre-rRNA subunits, indicating disturbed RNA processing. The family was 1 of 141 families in the cohort, thus accounting for 0.7%.
Ikeda et al. (2017) found that morpholino knockdown of the rps15a gene in zebrafish embryos resulted in abnormalities, including thin yolk sac, bent tail, and a markedly reduced erythrocyte production. The mutant phenotype could be rescued by expression of wildtype rps15a.
Ikeda, F., Yoshida, K., Toki, T., Uechi, T., Ishida, S., Nakajima, Y., Sasahara, Y., Okuno, Y., Kanezaki, R., Terui, K., Kamio, T., Kobayashi, A., and 14 others. Exome sequencing identified RPS15A as a novel causative gene for Diamond-Blackfan anemia. (Letter) Haematologica 102: e93-e96, 2017. Note: Electronic Article. [PubMed: 27909223] [Full Text: https://doi.org/10.3324/haematol.2016.153932]