| Affiliation: | 1. Imperial Molecular Pathology Laboratory, Imperial College Healthcare NHS Trust and Academic Health Sciences Centre, Hammersmith Hospital, , London, UK;2. Centre for Haematology, Faculty of Medicine, Imperial College London, Hammersmith Hospital, , London, UK;3. Imperial NIHR Biomedical Research Centre, Imperial College London, , London, UK;4. Genomics Laboratory, MRC Clinical Sciences Centre, Imperial College London, , London, UK;5. Pediatric Haematology and Bone Marrow Transplantation Unit, Department of Paediatrics, Imperial College Healthcare NHS Trust, , London, UK |
| Abstract: | Diamond‐Blackfan anaemia (DBA) is caused by inactivating mutations in ribosomal protein (RP) genes, with mutations in 13 of the 80 RP genes accounting for 50–60% of cases. The remaining 40–50% cases may harbour mutations in one of the remaining RP genes, but the very low frequencies render conventional genetic screening as challenging. We, therefore, applied custom enrichment technology combined with high‐throughput sequencing to screen all 80 RP genes. Using this approach, we identified and validated inactivating mutations in 15/17 (88%) DBA patients. Target enrichment combined with high‐throughput sequencing is a robust and improved methodology for the genetic diagnosis of DBA. |
