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Complexities of genetic diagnosis illustrated by an atypical case of congenital hypoplastic anemia
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 diagn...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6318771/ https://www.ncbi.nlm.nih.gov/pubmed/30559313 http://dx.doi.org/10.1101/mcs.a003384 |
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author | Claassen, David Boals, Michelle Bowling, Kevin M. Cooper, Gregory M. Cox, Jennifer Hershfield, Michael Lewis, Sara Wlodarski, Marcin Weiss, Mitchell J. Estepp, Jeremie H. |
author_facet | Claassen, David Boals, Michelle Bowling, Kevin M. Cooper, Gregory M. Cox, Jennifer Hershfield, Michael Lewis, Sara Wlodarski, Marcin Weiss, Mitchell J. Estepp, Jeremie H. |
author_sort | Claassen, David |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6318771 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-63187712019-01-13 Complexities of genetic diagnosis illustrated by an atypical case of congenital hypoplastic anemia Claassen, David Boals, Michelle Bowling, Kevin M. Cooper, Gregory M. Cox, Jennifer Hershfield, Michael Lewis, Sara Wlodarski, Marcin Weiss, Mitchell J. Estepp, Jeremie H. Cold Spring Harb Mol Case Stud Rapid Communication 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. Cold Spring Harbor Laboratory Press 2018-12 /pmc/articles/PMC6318771/ /pubmed/30559313 http://dx.doi.org/10.1101/mcs.a003384 Text en © 2018 Claassen et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/) , which permits reuse and redistribution, except for commercial purposes, provided that the original author and source are credited. |
spellingShingle | Rapid Communication Claassen, David Boals, Michelle Bowling, Kevin M. Cooper, Gregory M. Cox, Jennifer Hershfield, Michael Lewis, Sara Wlodarski, Marcin Weiss, Mitchell J. Estepp, Jeremie H. Complexities of genetic diagnosis illustrated by an atypical case of congenital hypoplastic anemia |
title | Complexities of genetic diagnosis illustrated by an atypical case of congenital hypoplastic anemia |
title_full | Complexities of genetic diagnosis illustrated by an atypical case of congenital hypoplastic anemia |
title_fullStr | Complexities of genetic diagnosis illustrated by an atypical case of congenital hypoplastic anemia |
title_full_unstemmed | Complexities of genetic diagnosis illustrated by an atypical case of congenital hypoplastic anemia |
title_short | Complexities of genetic diagnosis illustrated by an atypical case of congenital hypoplastic anemia |
title_sort | complexities of genetic diagnosis illustrated by an atypical case of congenital hypoplastic anemia |
topic | Rapid Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6318771/ https://www.ncbi.nlm.nih.gov/pubmed/30559313 http://dx.doi.org/10.1101/mcs.a003384 |
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