Spontaneous remission in a Diamond-Blackfan anaemia patient due to a revertant uniparental disomy ablating a de novo RPS19 mutation

A combination of multilevel molecular analyses including whole exome sequencing (WES), SNP-arrays, microsatellite segregations, and primer extensions allowed us to explain an unsolved case of remitted Diamond-Blackfan Anaemia (DBA). In the patient’s symptomatic DNA we identified a mosaic de novo pathogenic change, namely c.140C>T (p.Pro47Leu) in RPS19. We showed the mosaicism was due to the presence of a UniParental Disomy (UPD) involving the long arm of chromosome 19, where RPS19 is mapped. We demonstrated the remission was associated with a reduction of mutant cells, likely due to the positive selection of UPD clones, ablating the mutation.