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Basic Characteristics of Mutations
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Mutation Site
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C592G |
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Mutation Site Sentence
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C592G was present in all episodes of both cases and controls at frequencies <15%, but never induced. |
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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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UL97 |
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Standardized Encoding Gene
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UL97
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Genotype/Subtype
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- |
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Viral Reference
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X17403
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Functional Impact and Mechanisms
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Disease
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Cytomegalovirus infections
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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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(val)ganciclovir |
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Location
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- |
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Literature Information
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PMID
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34660835
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Title
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Development and Dynamics of Cytomegalovirus UL97 Ganciclovir Resistance Mutations in Transplant Recipients Detected by Next-Generation Sequencing
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Author
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Lodding IP,Jorgensen M,Bennedbaek M,Kirkby N,Naegele K,Gustafsson F,Perch M,Rasmussen A,Sengelov H,Sorensen SS,Hirsch HH,Lundgren JD
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Journal
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Open forum infectious diseases
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Journal Info
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2021 Sep 4;8(10):ofab462
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Abstract
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BACKGROUND: (Val)ganciclovir resistance mutations in CMV UL97 (UL97-GCV-R) complicate anti-CMV therapy in recipients of solid organ and hematopoietic stem cell transplants, but comprehensive data on prevalence, emergence, and outcome are scarce. METHODS: Using next-generation sequencing (NGS; Illumina MiSeq platform), we analyzed UL97-GCV-R in patients with available plasma samples and refractory CMV replication/DNAemia (n = 87) containing viral loads >/=910 IU/mL. Twenty-one patients with CMV DNAemia resolving under antiviral therapy were analyzed as controls. Detected mutations were considered induced and of potential clinical significance if they increased by >/=10% compared with the first detected frequency or if they had a maximum frequency >/=25%. RESULTS: Nineteen of 87 (21.8%) with refractory CMV replication had >/=1 UL97-GCV-R detected by NGS, in comparison to 0/21 of the controls (P = .02). One-third of the recipients had 2 or more induced UL97-GCV-R mutations. The most frequently induced mutations affected codons 595 (42% [8/19]), 594 (32% [6/19]), and 603 (32% [6/19]). C592G was present in all episodes of both cases and controls at frequencies <15%, but never induced. UL97-GCV-R tended to be more frequent in donor/recipient CMV immunoglobulin G mismatch or following failure to complete primary prophylaxis, and many developed invasive CMV disease. CONCLUSIONS: UL97-GCV-R is common among transplant patients with refractory CMV replication. Early testing by NGS allows for identification of major mutations at codons 595, 594, and 603 and excludes a major role of C592G in ganciclovir resistance. Large prospective studies on UL97-GCV-R are warranted.
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Sequence Data
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-
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