A rare case of acquired immunodeficiency associated with myelodysplastic syndrome
Abstract 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 investig...
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| Format: | Article |
| Language: | English |
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Wiley
2019-11-01
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| Series: | Molecular Genetics & Genomic Medicine |
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| Online Access: | https://doi.org/10.1002/mgg3.923 |
| _version_ | 1797296172926238720 |
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| author | Juanjuan Li Junhui Li Jianguo Li Hailan Yao Fang Liu James F Gusella Xiaodong Shi Xiaoli Chen |
| author_facet | Juanjuan Li Junhui Li Jianguo Li Hailan Yao Fang Liu James F Gusella Xiaodong Shi Xiaoli Chen |
| author_sort | Juanjuan Li |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-07T21:58:36Z |
| format | Article |
| id | doaj.art-e5cbd2c2f69643a491adea9f5029a250 |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-03-07T21:58:36Z |
| publishDate | 2019-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-e5cbd2c2f69643a491adea9f5029a2502024-02-24T07:01:11ZengWileyMolecular Genetics & Genomic Medicine2324-92692019-11-01711n/an/a10.1002/mgg3.923A rare case of acquired immunodeficiency associated with myelodysplastic syndromeJuanjuan Li0Junhui Li1Jianguo Li2Hailan Yao3Fang Liu4James F Gusella5Xiaodong Shi6Xiaoli Chen7Department of Hematology Affiliated Children’s Hospital of Capital Institute of Pediatrics Beijing ChinaDepartment of Hematology Affiliated Children’s Hospital of Capital Institute of Pediatrics Beijing ChinaDepartment of Rheumatology Affiliated Children’s Hospital of Capital Institute of Pediatrics Beijing ChinaDepartment of Molecular Immunology Capital Institute of Pediatrics Beijing ChinaDepartment of Medical Genetics, Beijing Municipal Key Laboratory of Child Development and Nutriomics Capital Institute of Pediatrics Beijing ChinaMolecular Neurogenetics Unit, Center for Genomic Medicine Massachusetts General Hospital Boston Massachusetts USADepartment of Hematology Affiliated Children’s Hospital of Capital Institute of Pediatrics Beijing ChinaDepartment of Medical Genetics, Beijing Municipal Key Laboratory of Child Development and Nutriomics Capital Institute of Pediatrics Beijing ChinaAbstract 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.https://doi.org/10.1002/mgg3.923acquired UPDimmunodeficiencymyelodysplastic syndromeRAG1 |
| spellingShingle | Juanjuan Li Junhui Li Jianguo Li Hailan Yao Fang Liu James F Gusella Xiaodong Shi Xiaoli Chen A rare case of acquired immunodeficiency associated with myelodysplastic syndrome Molecular Genetics & Genomic Medicine acquired UPD immunodeficiency myelodysplastic syndrome RAG1 |
| 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 | acquired UPD immunodeficiency myelodysplastic syndrome RAG1 |
| url | https://doi.org/10.1002/mgg3.923 |
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