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.

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

Garelli, Emanuela;Quarello, Paola;Giorgio, Elisa;Carando, Adriana;Menegatti, Elisa;Mancini, Cecilia;Di Gregorio, Eleonora;Ramenghi, Ugo;Brusco, Alfredo
2019

Abstract

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.
185
994
998
http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1365-2141
complete remission; Diamond-Blackfan; revertant mosaicism; RPS19; uniparental disomy; Hematology
Garelli, Emanuela; Quarello, Paola; Giorgio, Elisa; Carando, Adriana; Menegatti, Elisa; Mancini, Cecilia; Di Gregorio, Eleonora; Crescenzio, Nicoletta; Palumbo, Orazio; Carella, Massimo; Dimartino, Paola; Pippucci, Tommaso; Dianzani, Irma; Ramenghi, Ugo; Brusco, Alfredo
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/1692048
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