A 20-year long term experience of the Italian Diamond-Blackfan Anaemia Registry: RPS and RPL genes, different faces of the same disease?
Corresponding Author
Paola Quarello
Paediatric Onco-Haematology, Stem Cell Transplantation and Cellular Therapy Division, Regina Margherita Children's Hospital, Turin, Italy
Correspondence: Paola Quarello, Paediatric Onco-Haematology, Stem Cell Transplantation and Cellular Therapy Division, Regina Margherita Children's Hospital, Piazza Polonia 94, 10126, Torino, Italy.
E-mail: [email protected]
Search for more papers by this authorEmanuela Garelli
Department of Public Health and Paediatric Sciences, University of Torino, Turin, Italy
Search for more papers by this authorAdriana Carando
Department of Public Health and Paediatric Sciences, University of Torino, Turin, Italy
Search for more papers by this authorRebecca Cillario
Department of Public Health and Paediatric Sciences, University of Torino, Turin, Italy
Search for more papers by this authorAlfredo Brusco
Department of Medical Sciences, University of Torino, Turin, Italy
Medical Genetics Unit, “Città della Salute e della Scienza” Hospital, Turin, Italy
Search for more papers by this authorElisa Giorgio
Department of Medical Sciences, University of Torino, Turin, Italy
Search for more papers by this authorDaniela Ferrante
Department of Translational Medicine, Unit of Cancer Epidemiology, CPO-Piemonte, University of Eastern Piedmont, Novara, Italy
Search for more papers by this authorPaola Corti
Paediatric Haematology, Fondazione MBBM, Monza, Italy
Search for more papers by this authorMarco Zecca
Department of Paediatric Haematology/Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
Search for more papers by this authorMatteo Luciani
Haemostasis and Thrombosis Center, Onco-Haematology Department, Bambino Gesù Paediatric Hospital, Rome, Italy
Search for more papers by this authorFilomena Pierri
Clinical and Experimental Unit, G. Gaslini Children's Hospital, Genoa, Italy
Search for more papers by this authorMaria C. Putti
Department of Women’s and Children’s Health, Paediatric Haematology-Oncology Unit, University of Padova, Padua, Italy
Search for more papers by this authorMaria E. Cantarini
Paediatric Oncology and Haematology, U.O. Pediatria, Department of Women’s and Children’s Health, Policlinico Azienda Ospedaliera Universitaria Sant’Orsola Malpighi, Bologna, Italy
Search for more papers by this authorPiero Farruggia
Paediatric Haematology and Oncology Unit, A.R.N.A. S. Ospedale Civico, Palermo, Italy
Search for more papers by this authorAngelica Barone
Department of Paediatric Onco-Haematology, University Hospital, Parma, Italy
Search for more papers by this authorSimone Cesaro
Paediatric Haematology Oncology, Ospedale Donna Bambino, Azienda Ospedaliera Universitaria Integrata, Verona, Italy
Search for more papers by this authorGiovanna Russo
Paediatric Haematology and Oncology Unit, Azienda Policlinico-Vittorio Emanuele, University of Catania, Catania, Italy
Search for more papers by this authorFranca Fagioli
Paediatric Onco-Haematology, Stem Cell Transplantation and Cellular Therapy Division, Regina Margherita Children's Hospital, Turin, Italy
Department of Public Health and Paediatric Sciences, University of Torino, Turin, Italy
Search for more papers by this authorIrma Dianzani
Department of Health Sciences, University of Eastern Piedmont, Novara, Italy
Search for more papers by this authorUgo Ramenghi
Department of Public Health and Paediatric Sciences, University of Torino, Turin, Italy
Search for more papers by this authorthe AIEOP working group on Diamond Blackfan Anaemia
Search for more papers by this authorCorresponding Author
Paola Quarello
Paediatric Onco-Haematology, Stem Cell Transplantation and Cellular Therapy Division, Regina Margherita Children's Hospital, Turin, Italy
Correspondence: Paola Quarello, Paediatric Onco-Haematology, Stem Cell Transplantation and Cellular Therapy Division, Regina Margherita Children's Hospital, Piazza Polonia 94, 10126, Torino, Italy.
E-mail: [email protected]
Search for more papers by this authorEmanuela Garelli
Department of Public Health and Paediatric Sciences, University of Torino, Turin, Italy
Search for more papers by this authorAdriana Carando
Department of Public Health and Paediatric Sciences, University of Torino, Turin, Italy
Search for more papers by this authorRebecca Cillario
Department of Public Health and Paediatric Sciences, University of Torino, Turin, Italy
Search for more papers by this authorAlfredo Brusco
Department of Medical Sciences, University of Torino, Turin, Italy
Medical Genetics Unit, “Città della Salute e della Scienza” Hospital, Turin, Italy
Search for more papers by this authorElisa Giorgio
Department of Medical Sciences, University of Torino, Turin, Italy
Search for more papers by this authorDaniela Ferrante
Department of Translational Medicine, Unit of Cancer Epidemiology, CPO-Piemonte, University of Eastern Piedmont, Novara, Italy
Search for more papers by this authorPaola Corti
Paediatric Haematology, Fondazione MBBM, Monza, Italy
Search for more papers by this authorMarco Zecca
Department of Paediatric Haematology/Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
Search for more papers by this authorMatteo Luciani
Haemostasis and Thrombosis Center, Onco-Haematology Department, Bambino Gesù Paediatric Hospital, Rome, Italy
Search for more papers by this authorFilomena Pierri
Clinical and Experimental Unit, G. Gaslini Children's Hospital, Genoa, Italy
Search for more papers by this authorMaria C. Putti
Department of Women’s and Children’s Health, Paediatric Haematology-Oncology Unit, University of Padova, Padua, Italy
Search for more papers by this authorMaria E. Cantarini
Paediatric Oncology and Haematology, U.O. Pediatria, Department of Women’s and Children’s Health, Policlinico Azienda Ospedaliera Universitaria Sant’Orsola Malpighi, Bologna, Italy
Search for more papers by this authorPiero Farruggia
Paediatric Haematology and Oncology Unit, A.R.N.A. S. Ospedale Civico, Palermo, Italy
Search for more papers by this authorAngelica Barone
Department of Paediatric Onco-Haematology, University Hospital, Parma, Italy
Search for more papers by this authorSimone Cesaro
Paediatric Haematology Oncology, Ospedale Donna Bambino, Azienda Ospedaliera Universitaria Integrata, Verona, Italy
Search for more papers by this authorGiovanna Russo
Paediatric Haematology and Oncology Unit, Azienda Policlinico-Vittorio Emanuele, University of Catania, Catania, Italy
Search for more papers by this authorFranca Fagioli
Paediatric Onco-Haematology, Stem Cell Transplantation and Cellular Therapy Division, Regina Margherita Children's Hospital, Turin, Italy
Department of Public Health and Paediatric Sciences, University of Torino, Turin, Italy
Search for more papers by this authorIrma Dianzani
Department of Health Sciences, University of Eastern Piedmont, Novara, Italy
Search for more papers by this authorUgo Ramenghi
Department of Public Health and Paediatric Sciences, University of Torino, Turin, Italy
Search for more papers by this authorthe AIEOP working group on Diamond Blackfan Anaemia
Search for more papers by this authorSummary
Diamond–Blackfan anaemia (DBA) is a rare and heterogeneous disease characterised by hypoplastic anaemia, congenital anomalies and a predisposition for malignancies. The aim of this paper is to report the findings from the Italian DBA Registry, and to discuss the Registry’s future challenges in tackling this disease. Our 20-year long work allowed the connection of 50 Italian Association of Paediatric Haematology and Oncology (AIEOP) centres and the recruitment of 283 cases. Almost all patients have been characterised at a molecular level (96%, 271/283), finding a causative mutation in 68% (184/271). We confirm the importance of determination of erythrocyte adenosine deaminase activity (eADA) and of ribosomal RNA assay in the diagnostic pipeline and characterisation of a remission state. Patients with mutations in large ribosomal subunit protein (RPL) genes had a significant correlation with the incidence of malformations, higher eADA levels and more severe outcomes, compared to patients with mutations in small ribosomal subunit protein (RPS) genes. Furthermore, as a consequence of our findings, particularly the incidence of malignancies and the high percentage of patients aged >18 years, we stress the importance of collaboration with adult clinicians to guarantee regular multi-specialist follow-up. In conclusion, this study highlights the importance of national registries to increase our understanding and improve management of this complex disease.
Supporting Information
| Filename | Description |
|---|---|
| bjh16508-sup-0001-FigS1.tifTIFF image, 83.8 MB |
Fig S1. DBA registry structure. The DBA Registry is coordinated by the Turin AIEOP Centre and involves a network of 50 AIEOP centres in Italy. At diagnosis, each patient is registered onto Mod.1.01, after having parents or a guardian’s informed consent, and after being identified by a Unique Patient Number (UPN). All patients’ personal data are not viewable except for responsible clinicians. Through the UPN, the patient can then be assigned to the DBA Registry. All information is loaded by the responsible clinician at each AIEOP Centre. Genetic analyses are performed following a standard workflow in a central laboratory and result analyses are inserted into the DBA database. The referral centre requires an annual update of the follow-up section. |
| bjh16508-sup-0002-FigS2.tifTIFF image, 81.4 MB |
Fig S2. Patient distribution by birth year. |
| bjh16508-sup-0003-FigS3.tifTIFF image, 67.1 MB |
Fig S3. Analysis of survival in patients with DBA by treatment response. Dash line: REM (patients in sustained remission), dotted line: SD (patients maintainable on corticosteroids), continuous line: TD (transfusion-dependent patients). |
| bjh16508-sup-0004-TableS1.docxWord document, 14.6 KB |
Table S1. Congenital anomalies in DBA patients. |
| bjh16508-sup-0005-AppendixS1.docxWord document, 14.4 KB |
Appendix S1. AIEOP working group on Diamond Blackfan Anaemia. |
| bjh16508-sup-0006-DataS1.docxWord document, 15.2 KB |
Data S1. Supplementary data. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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