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Basic Characteristics of Mutations
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Mutation Site
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G212S |
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Mutation Site Sentence
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The presence of both G212S and S366T carries a nearly 12-fold increased risk of development of EBV-positive PTLD. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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LMP-1 |
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Standardized Encoding Gene
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LMP-1
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Genotype/Subtype
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- |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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Lymphoproliferative Disorders
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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Y |
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Treatment
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- |
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Location
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USA |
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Literature Information
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PMID
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36796762
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Title
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Mutations in latent membrane protein 1 of Epstein-Barr virus are associated with increased risk of posttransplant lymphoproliferative disorder in children
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Author
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Martinez OM,Krams SM,Robien MA,Lapasaran MG,Arvedson MP,Reitsma A,Balachandran Y,Harris-Arnold A,Weinberg K,Boyd SD,Armstrong B,Trickey A,Twist CJ,Gratzinger D,Tan B,Brown M,Chin C,Desai DM,Fishbein TM,Mazariegos GV,Tekin A,Venick RS,Bernstein D,Esquivel CO
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Journal
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American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
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Journal Info
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2023 May;23(5):611-618
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Abstract
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Epstein-Barr virus (EBV)-positive posttransplant lymphoproliferative disorder (PTLD) results in significant morbidity and mortality in pediatric transplant recipients. Identifying individuals at an increased risk of EBV-positive PTLD could influence clinical management of immunosuppression and other therapies, improving posttransplant outcomes. A 7-center prospective, observational clinical trial of 872 pediatric transplant recipients evaluated the presence of mutations at positions 212 and 366 of EBV latent membrane protein 1 (LMP1) as an indicator of risk of EBV-positive PTLD (clinical trials: NCT02182986). DNA was isolated from peripheral blood of EBV-positive PTLD case patients and matched controls (1:2 nested case:control), and the cytoplasmic tail of LMP1 was sequenced. Thirty-four participants reached the primary endpoint of biopsy-proven EBV-positive PTLD. DNA was sequenced from 32 PTLD case patients and 62 matched controls. Both LMP1 mutations were present in 31 of 32 PTLD cases (96.9%) and in 45 of 62 matched controls (72.6%) (P = .005; OR = 11.7; 95% confidence interval, 1.5, 92.6). The presence of both G212S and S366T carries a nearly 12-fold increased risk of development of EBV-positive PTLD. Conversely, transplant recipients without both LMP1 mutations carry a very low risk of PTLD. Analysis of mutations at positions 212 and 366 of LMP1 can be informative in stratifying patients for risk of EBV-positive PTLD.
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Sequence Data
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-
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