Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Claassen, David, Boals, Michelle, Bowling, Kevin M., Cooper, Gregory M., Cox, Jennifer, Hershfield, Michael, Lewis, Sara, Wlodarski, Marcin, Weiss, Mitchell J., Estepp, Jeremie H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2018
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
_version_ 1783384945802084352
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
work_keys_str_mv AT claassendavid complexitiesofgeneticdiagnosisillustratedbyanatypicalcaseofcongenitalhypoplasticanemia
AT boalsmichelle complexitiesofgeneticdiagnosisillustratedbyanatypicalcaseofcongenitalhypoplasticanemia
AT bowlingkevinm complexitiesofgeneticdiagnosisillustratedbyanatypicalcaseofcongenitalhypoplasticanemia
AT coopergregorym complexitiesofgeneticdiagnosisillustratedbyanatypicalcaseofcongenitalhypoplasticanemia
AT coxjennifer complexitiesofgeneticdiagnosisillustratedbyanatypicalcaseofcongenitalhypoplasticanemia
AT hershfieldmichael complexitiesofgeneticdiagnosisillustratedbyanatypicalcaseofcongenitalhypoplasticanemia
AT lewissara complexitiesofgeneticdiagnosisillustratedbyanatypicalcaseofcongenitalhypoplasticanemia
AT wlodarskimarcin complexitiesofgeneticdiagnosisillustratedbyanatypicalcaseofcongenitalhypoplasticanemia
AT weissmitchellj complexitiesofgeneticdiagnosisillustratedbyanatypicalcaseofcongenitalhypoplasticanemia
AT esteppjeremieh complexitiesofgeneticdiagnosisillustratedbyanatypicalcaseofcongenitalhypoplasticanemia