Targeted next generation sequencing for the diagnosis of patients with rare congenital anemias

Noa Shefer Averbuch, Orna Steinberg-Shemer, Orly Dgany, Tanya Krasnov, Sharon Noy-Lotan, Joanne Yacobovich, Amir A. Kuperman, Antonis Kattamis, Ayelet Ben Barak, Batia Roth-Jelinek, Evgeni Chubar, Evelyn Shabad, Gustavo Dufort, Martin Ellis, Ofir Wolach, Idit Pazgal, Abed Abu Quider, Hagit Miskin, Hannah Tamary

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


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.

Original languageEnglish
Pages (from-to)297-304
Number of pages8
JournalEuropean Journal of Haematology
Issue number3
StatePublished - Sep 2018

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© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd


  • red cell disorders


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