European journal of haematology, 2018-09, Vol.101 (3), p.297-304
2018
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- Autor(en) / Beteiligte
- Titel
- Targeted next generation sequencing for the diagnosis of patients with rare congenital anemias
- Ist Teil von
- European journal of haematology, 2018-09, Vol.101 (3), p.297-304
- Ort / Verlag
- England: Wiley Subscription Services, Inc
- Erscheinungsjahr
- 2018
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Background Most patients with anemia are diagnosed through clinical phenotype and basic laboratory testing. Nonetheless, in cases of rare congenital anemias, some patients remain undiagnosed despite undergoing an exhaustive workup. Genetic testing is complicated by the large number of genes involved in rare anemias and the similarities in the clinical presentation of the different syndromes. Objective We aimed to enhance the diagnosis of patients with congenital anemias by using targeted next‐generation sequencing. Methods Genetic diagnosis was performed by gene capture followed by next‐generation sequencing of 76 genes known to cause anemia syndromes. Results Genetic diagnosis was achieved in 13 out of 21 patients (62%). Six patients were diagnosed with pyruvate kinase deficiency, 4 with dehydrated hereditary stomatocytosis, 2 with sideroblastic anemia, and 1 with CDA type IV. Eight novel mutations were found. In 7 patients, the genetic diagnosis differed from the pretest presumed diagnosis. The mean lag time from presentation to diagnosis was over 13 years. Conclusions Targeted next‐generation sequencing led to an accurate diagnosis in over 60% of patients with rare anemias. These patients do not need further diagnostic workup. Earlier incorporation of this method into the workup of patients with congenital anemia may improve patients’ care and enable genetic counseling.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0902-4441eISSN: 1600-0609DOI: 10.1111/ejh.13097Titel-ID: cdi_proquest_miscellaneous_2042751549
- Format
- –
- Schlagworte
- Adolescent, Adult, Anemia, Anemia - blood, Anemia - congenital, Anemia - diagnosis, Anemia - therapy, Anemia, Dyserythropoietic, Congenital - diagnosis, Anemia, Dyserythropoietic, Congenital - genetics, Anemia, Dyserythropoietic, Congenital - therapy, Anemia, Hemolytic, Congenital - diagnosis, Anemia, Hemolytic, Congenital - genetics, Anemia, Hemolytic, Congenital Nonspherocytic - diagnosis, Anemia, Hemolytic, Congenital Nonspherocytic - genetics, Anemia, Sideroblastic - diagnosis, Anemia, Sideroblastic - genetics, Bone Marrow - pathology, Child, Child, Preschool, Computational Biology, Diagnosis, Erythrocyte Indices, Female, Genetic Association Studies, Genetic counseling, Genetic Predisposition to Disease, Genetic screening, Genetic Testing, High-Throughput Nucleotide Sequencing, Humans, Hydrops Fetalis - diagnosis, Hydrops Fetalis - genetics, Kinases, Male, Mutation, Phenotypes, Pyruvate kinase, Pyruvate Kinase - deficiency, Pyruvate Kinase - genetics, Pyruvate Metabolism, Inborn Errors - diagnosis, Pyruvate Metabolism, Inborn Errors - genetics, Pyruvic acid, Rare Diseases, red cell disorders, Sideroblastic anemia, Young Adult