Complexities of genetic diagnosis illustrated by an atypical case of congenital hypoplastic anemia

David Claassen, Michelle Boals, Kevin M. Bowling, Gregory M. Cooper, Jennifer Cox, Michael Hershfield, Sara Lewis, Marcin Wlodarski, Mitchell J. Weiss, Jeremie H. Estepp

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12 Scopus citations


Diamond-Blackfan Anemia (DBA) is a rare polygenic disorder defined by congenital hypoplastic anemia with marked decrease or absence of bone marrow erythroid precursors. Identifying the specific genetic etiology is important for counseling and clinical management. A 6-yr-old boy with a clinical diagnosis of DBA has been followed by our pediatric hematology team since birth. His clinical course includes transfusion-dependent hypoplastic anemia and progressive autoimmune cytopenias. Genetic testing failed to identify a causative mutation in any of the classical DBA-associated genes. He and his parents underwent trio whole-exome sequencing (WES) with no genetic etiology identified initially. Clinical persistence and suspicion led to testing for adenosine deaminase 2 (ADA2) activity and whole-genome sequencing (WGS) that identified compound heterozygous pathogenic mutations in the ADA2-encoding CECR1 gene, a recently appreciated etiology for congenital hypoplastic anemia. This case illustrates current challenges in genetic testing and how they can be overcome by multidisciplinary expertise in clinical medicine and genomics.

Original languageEnglish
Article numbera003384
JournalCold Spring Harbor molecular case studies
Issue number6
StatePublished - Dec 2018


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