Czech and Slovak Diamond-Blackfan Anemia (DBA) Registry update: Clinical data and novel causative genetic lesions
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
31855845
DOI
10.1016/j.bcmd.2019.102380
PII: S1079-9796(19)30278-5
Knihovny.cz E-resources
- Keywords
- Cancer, Diamond-Blackfan anemia (DBA), Mutations, Registry, Ribosomal proteins (RP),
- MeSH
- Anemia, Diamond-Blackfan complications epidemiology genetics MeSH
- Genetic Association Studies MeSH
- Humans MeSH
- Mutation * MeSH
- Neoplasms etiology MeSH
- Registries MeSH
- Ribosomal Proteins genetics MeSH
- Family MeSH
- Exome Sequencing MeSH
- Comparative Genomic Hybridization MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Czech Republic MeSH
- Slovakia MeSH
- Names of Substances
- ribosomal protein L11 MeSH Browser
- ribosomal protein L5, human MeSH Browser
- ribosomal protein S19 MeSH Browser
- Ribosomal Proteins MeSH
Diamond-Blackfan anemia (DBA) is a rare congenital erythroid aplasia, underlied by haploinsufficient mutations in genes coding for ribosomal proteins (RP) in approximately 70% of cases. DBA is frequently associated with somatic malformations, endocrine dysfunction and with an increased predisposition to cancer. Here we present clinical and genetic characteristics of 62 patients from 52 families enrolled in the Czech and Slovak DBA Registry. Whole exome sequencing (WES) and array comparative genomic hybridization (aCGH) were employed to identify causative mutations in newly diagnosed patients and in cases with previously unrecognized molecular pathology. RP mutation detection rate was 81% (50/62 patients). This included 8 novel point mutations and 4 large deletions encompassing some of the RP genes. Malignant or predisposing condition developed in 8/62 patients (13%): myelodysplastic syndrome in 3 patients; breast cancer in 2 patients; colorectal cancer plus ocular tumor, diffuse large B-cell lymphoma and multiple myeloma each in one case. These patients exclusively harbored RPL5, RPL11 or RPS19 mutations. Array CGH is beneficial for detection of novel mutations in DBA due to its capacity to detect larger chromosomal aberrations. Despite the importance of genotype-phenotype correlation in DBA, phenotypic differences among family members harboring an identical mutation were observed.
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