Target enrichment and high‐throughput sequencing of 80 ribosomal protein genes to identify mutations associated with Diamond‐Blackfan anaemia

Summary 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 c...

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Bibliographic Details
Published in:British journal of haematology 2013-08, Vol.162 (4), p.530-536
Main Authors: Gerrard, Gareth, Valgañón, Mikel, Foong, Hui En, Kasperaviciute, Dalia, Iskander, Deena, Game, Laurence, Müller, Michael, Aitman, Timothy J., Roberts, Irene, Fuente, Josu, Foroni, Letizia, Karadimitris, Anastasios
Format: Article
Language:English
Subjects:
Adolescent
Adult
Anemia, Diamond-Blackfan - genetics
Anemias. Hemoglobinopathies
Biological and medical sciences
Child
Child, Preschool
Codon, Nonsense
Diamond‐Blackfan anaemia
Diseases of red blood cells
DNA Mutational Analysis
DNA, Ribosomal - blood
DNA, Ribosomal - genetics
Female
Frameshift Mutation
Gene Library
Hematologic and hematopoietic diseases
High-Throughput Nucleotide Sequencing
Humans
Male
Medical sciences
molecular diagnostics
next generation sequencing
Ribosomal Proteins - genetics
Sequence Alignment
Sequence Analysis, DNA
Sequence Deletion
target enrichment
Tumors
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Summary:Summary 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.
ISSN:0007-1048
1365-2141
DOI:10.1111/bjh.12397