Journal article
Complexities of genetic diagnosis illustrated by an atypical case of congenital hypoplastic anemia
Cold Spring Harbor molecular case studies, Vol.4(6), p.a003384
12/01/2018
DOI: 10.1101/mcs.a003384
PMCID: PMC6318771
PMID: 30559313
Abstract
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.
Details
- Title: Subtitle
- Complexities of genetic diagnosis illustrated by an atypical case of congenital hypoplastic anemia
- Creators
- David Claassen - St. Jude Children's Research HospitalMichelle Boals - St. Jude Children's Research HospitalKevin M. Bowling - HudsonAlpha Institute for BiotechnologyGregory M. Cooper - HudsonAlpha Institute for BiotechnologyJennifer Cox - Huntsville HospitalMichael Hershfield - Duke UniversitySara Lewis - St. Jude Children's Research HospitalMarcin Wlodarski - St. Jude Children's Research HospitalMitchell J. Weiss - St. Jude Children's Research HospitalJeremie H. Estepp - St. Jude Children's Research Hospital
- Resource Type
- Journal article
- Publication Details
- Cold Spring Harbor molecular case studies, Vol.4(6), p.a003384
- DOI
- 10.1101/mcs.a003384
- PMID
- 30559313
- PMCID
- PMC6318771
- NLM abbreviation
- Cold Spring Harb Mol Case Stud
- ISSN
- 2373-2873
- eISSN
- 2373-2873
- Publisher
- Cold Spring Harbor Lab Press, Publications Dept
- Number of pages
- 6
- Grant note
- American Lebanese Syrian Associated Charities (ALSAC)
- Language
- English
- Date published
- 12/01/2018
- Academic Unit
- Stead Family Department of Pediatrics; Hematology/Oncology
- Record Identifier
- 9984354036602771
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