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A rare case of acquired immunodeficiency associated with myelodysplastic syndrome
BACKGROUND: Pediatric myelodysplastic syndromes (MDS) display clonal genomic instability that can lead to acquisition of other hematological disorders, usually by loss of heterozygosity. Immunodeficiency caused by uniparental disomy (UPD) has not previously been reported. METHODS: We investigated a...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825869/ https://www.ncbi.nlm.nih.gov/pubmed/31503426 http://dx.doi.org/10.1002/mgg3.923 |
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author | Li, Juanjuan Li, Junhui Li, Jianguo Yao, Hailan Liu, Fang Gusella, James F Shi, Xiaodong Chen, Xiaoli |
author_facet | Li, Juanjuan Li, Junhui Li, Jianguo Yao, Hailan Liu, Fang Gusella, James F Shi, Xiaodong Chen, Xiaoli |
author_sort | Li, Juanjuan |
collection | PubMed |
description | BACKGROUND: Pediatric myelodysplastic syndromes (MDS) display clonal genomic instability that can lead to acquisition of other hematological disorders, usually by loss of heterozygosity. Immunodeficiency caused by uniparental disomy (UPD) has not previously been reported. METHODS: We investigated a 13‐year‐old boy who suffered from recurrent infections and pancytopenia for 1 year. Both the comet assay and chromosome breakage analysis were normal, but the bone marrow showed evidence of dysplasia characteristic of MDS. With his normal sister as donor, he underwent failed hematopoietic stem cell transplantation (HSCT) with reduced intensity conditioning (RIC) followed by successful HSCT with myeloablative conditioning (MAC). We used single nucleotide polymorphism (SNP) array, targeted gene panel, and whole exome sequencing to investigate the etiology of his disease. RESULTS: The molecular analyses revealed multiple regions of homozygosity, one region encompassing a homozygous missense variant of recombination activating gene 1 (RAG1) which was previously associated with severe immunodeficiency in infancy. This RAG1 mutation was heterozygous in the proband’s fingernail DNA, but was changed to homozygous in the proband’s marrow by somatic acquisition of UPD event. No other pathogenic driver mutation for MDS‐related genes was identified. CONCLUSION: The hematological phenotype, somatic genomic instability, and response to HSCT MAC but not HSCT RIC deduced to a diagnosis of MDS type refractory cytopenia of children in this patient. His immunodeficiency was secondary to MDS due to somatic acquisition of homozygosity for known pathogenic RAG1 mutation. |
format | Online Article Text |
id | pubmed-6825869 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-68258692019-11-07 A rare case of acquired immunodeficiency associated with myelodysplastic syndrome Li, Juanjuan Li, Junhui Li, Jianguo Yao, Hailan Liu, Fang Gusella, James F Shi, Xiaodong Chen, Xiaoli Mol Genet Genomic Med Original Articles BACKGROUND: Pediatric myelodysplastic syndromes (MDS) display clonal genomic instability that can lead to acquisition of other hematological disorders, usually by loss of heterozygosity. Immunodeficiency caused by uniparental disomy (UPD) has not previously been reported. METHODS: We investigated a 13‐year‐old boy who suffered from recurrent infections and pancytopenia for 1 year. Both the comet assay and chromosome breakage analysis were normal, but the bone marrow showed evidence of dysplasia characteristic of MDS. With his normal sister as donor, he underwent failed hematopoietic stem cell transplantation (HSCT) with reduced intensity conditioning (RIC) followed by successful HSCT with myeloablative conditioning (MAC). We used single nucleotide polymorphism (SNP) array, targeted gene panel, and whole exome sequencing to investigate the etiology of his disease. RESULTS: The molecular analyses revealed multiple regions of homozygosity, one region encompassing a homozygous missense variant of recombination activating gene 1 (RAG1) which was previously associated with severe immunodeficiency in infancy. This RAG1 mutation was heterozygous in the proband’s fingernail DNA, but was changed to homozygous in the proband’s marrow by somatic acquisition of UPD event. No other pathogenic driver mutation for MDS‐related genes was identified. CONCLUSION: The hematological phenotype, somatic genomic instability, and response to HSCT MAC but not HSCT RIC deduced to a diagnosis of MDS type refractory cytopenia of children in this patient. His immunodeficiency was secondary to MDS due to somatic acquisition of homozygosity for known pathogenic RAG1 mutation. John Wiley and Sons Inc. 2019-09-10 /pmc/articles/PMC6825869/ /pubmed/31503426 http://dx.doi.org/10.1002/mgg3.923 Text en © 2019 Capital Institute of Pediatrics. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Original Articles Li, Juanjuan Li, Junhui Li, Jianguo Yao, Hailan Liu, Fang Gusella, James F Shi, Xiaodong Chen, Xiaoli A rare case of acquired immunodeficiency associated with myelodysplastic syndrome |
title | A rare case of acquired immunodeficiency associated with myelodysplastic syndrome |
title_full | A rare case of acquired immunodeficiency associated with myelodysplastic syndrome |
title_fullStr | A rare case of acquired immunodeficiency associated with myelodysplastic syndrome |
title_full_unstemmed | A rare case of acquired immunodeficiency associated with myelodysplastic syndrome |
title_short | A rare case of acquired immunodeficiency associated with myelodysplastic syndrome |
title_sort | rare case of acquired immunodeficiency associated with myelodysplastic syndrome |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825869/ https://www.ncbi.nlm.nih.gov/pubmed/31503426 http://dx.doi.org/10.1002/mgg3.923 |
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