Evidence map›Paper›PMID 41724404›Full record

ArticleThe Journal of allergy and clinical immunology2026

Clinical relevance of mosaic variants detected by exome sequencing.

Rajarshi Ghosh, Zeeshan Fazal, Andrew J Oler, Mari J Tokita, Katie L Lewis, Alexander J Paul, Elizabeth G Schmitz, Nermina Saucier, Jia Yan, Michael Kamen and 26 more

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In one paragraph

Article in The Journal of allergy and clinical immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

36 authors.

Rajarshi GhoshCentralized Sequencing Program, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Md. Electronic address: rajarshi.ghosh@nih.gov.
Zeeshan FazalBioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, NIAID, NIH, Bethesda, Md.
Andrew J OlerBioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, NIAID, NIH, Bethesda, Md.
Mari J TokitaCentralized Sequencing Program, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Md.
Katie L LewisCentralized Sequencing Program, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Md.
Alexander J PaulDepartment of Pediatrics, Division of Rheumatology & Immunology, Washington University School of Medicine in St Louis, St Louis, Mo.
Elizabeth G SchmitzDepartment of Pediatrics, Division of Rheumatology & Immunology, Washington University School of Medicine in St Louis, St Louis, Mo.
Nermina SaucierDepartment of Pediatrics, Division of Rheumatology & Immunology, Washington University School of Medicine in St Louis, St Louis, Mo.
Jia YanCentralized Sequencing Program, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Md.
Michael KamenCentralized Sequencing Program, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Md.
Bryce A SeifertCentralized Sequencing Program, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Md.
NIAID Centralized Sequencing Program,
Amy D KlionHuman Eosinophil Section, Laboratory of Parasitic Diseases, NIAID, NIH, Bethesda, Md.
Paneez KhouryHuman Eosinophil Section, Laboratory of Parasitic Diseases, NIAID, NIH, Bethesda, Md.
Ottavia M DelmonteImmune Deficiency Genetics Diseases Section, Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, Md.
Luigi D NotarangeloImmune Deficiency Genetics Diseases Section, Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, Md.
Alexandra F FreemanImmunopathogenesis Section, Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, Md.
Christa S ZerbeImmunopathogenesis Section, Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, Md.
Gulbu UzelImmunopathogenesis Section, Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, Md.
Dean D MetcalfeMast Cell Biology Section, Laboratory of Allergic Diseases, NIAID, NIH, Bethesda, Md.
Hirsh D KomarowMast Cell Biology Section, Laboratory of Allergic Diseases, NIAID, NIH, Bethesda, Md.
Melody C CarterMast Cell Biology Section, Laboratory of Allergic Diseases, NIAID, NIH, Bethesda, Md.
David H McDermottMolecular Signaling Section, Laboratory of Molecular Immunology, NIAID, NIH, Bethesda, Md.
Philip M MurphyMolecular Signaling Section, Laboratory of Molecular Immunology, NIAID, NIH, Bethesda, Md.
Kenneth N OlivierDivision of Pulmonary Diseases and Critical Care Medicine, University of North Carolina, Chapel Hill, NC.
Ivan FussMucosal Immunity Section, Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, Md.
Warren StroberMucosal Immunity Section, Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, Md.
V Koneti RaoPrimary Immune Deficiency Clinic (ALPS Clinic), Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, Md.
Jenna R E BergersonPrimary Immune Deficiency Clinic, Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, Md.
Adriana Almeida de JesusTranslational Autoinflammatory Disease Studies Unit, Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, Md.
Raphaela Goldbach-ManskyTranslational Autoinflammatory Disease Studies Unit, Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, Md.
Waleed Al-HerzDepartment of Pediatrics, College of Medicine, Kuwait University, Kuwait City, Kuwait.
Steven M HollandImmunopathogenesis Section, Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, Md.
Megan A CooperDepartment of Pediatrics, Division of Rheumatology & Immunology, Washington University School of Medicine in St Louis, St Louis, Mo.
Morgan N SimilukCentralized Sequencing Program, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Md.
Magdalena A WalkiewiczCentralized Sequencing Program, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Md.

Funding

Washington University Center for Cellular ImagingP30CA091842 · NCI · WASHINGTON UNIVERSITY · PI TIMOTHY J. EBERLEIN · 2001 to 2026
$128.0M
TRAINING PROGRAM IN IMMUNOLOGY AND IMMUNOGENETICST32AI007163 · NIAID · WASHINGTON UNIVERSITY · PI Kenneth M Murphy, Kodi S Ravichandran · 1985 to 2026
$14.8M
Somatic variants as drivers of genetic errors of immunityP01AI186771 · NIAID · WASHINGTON UNIVERSITY · PI Joshua D. Milner · 2025 to 2026
$7.5M
Human ISG15 and USP18 Deficiencies Underlying Type I InterferonopathiesR01AI127372 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Dusan Bogunovic · 2017 to 2026
$4.7M
Immunologic and Predictive Features of MIS-CR01HD108467 · NICHD · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Dusan Bogunovic · 2022 to 2026
$2.7M
Inborn Errors of Immunity Leading to Autoinflammatory SyndromesR01AI148963 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI BOGUNOVIC, DUSAN · 2020 to 2024
$2.5M
Genetic Mosaicism in Inborn Errors of ImmunityR21AI168957 · NIAID · WASHINGTON UNIVERSITY · PI COOPER, MEGAN ANNE · 2022 to 2023
$433k
Intramural NIH HHS Z99 AI999999NCI NIH HHS P30 CA091842NIAID NIH HHS P01 AI186771NIAID NIH HHS R01 AI127372NIAID NIH HHS R01 AI148963NIAID NIH HHS R21 AI168957NIAID NIH HHS T32 AI007163NICHD NIH HHS R01 HD108467
6 · The paper itself

Abstract

backgroundMosaic variants represent a significant but underrecognized contributor to human disease such as cancer and immune diseases. Despite advances in genetic diagnostics, mosaic variant detection remains challenging as a result of low variant allele fractions, tissue specificity, and clinical heterogeneity.

objectiveWe investigated the prevalence, diagnostic impact, and clinical relevance of mosaic variants in participants with immune disorders.

methodsExome sequencing of blood and/or saliva was performed in 2655 participants, including 2064 affected participants. Mosaic variants were detected using two algorithms, LoFreq2 and Mutect2. A subset of the detected variants was orthogonally validated. Clinical data were retrospectively analyzed to assess the clinical significance of these variants.

resultsMosaic variants associated with immune disorders contributed to a molecular diagnosis in 29 (1.4%) of 2064 affected participants. Notably, 9 (31%) of 29 of diagnostic variants were missed by standard germline analysis as a result of low variant allele fractions. Clinically relevant parental mosaicism was ascertained in two families. Enrichment of mosaic variants was observed in clonal hematopoiesis-related genes driven by older age and GATA2 deficiency, with prognostic implications for hematologic disorders. Finally, chemotherapy drug resistance variants in NRAS, KRAS, and IDH2 were identified, demonstrating the potential for mosaic variant detection to inform treatment strategies.

conclusionMosaic variants contribute significantly to the molecular diagnosis and prognosis of immune and hematologic disorders and are missed by typical germline variant-calling workflow.

Indexed as

MosaicismAdolescentAdultAgedChildChild, PreschoolExome SequencingFemaleHumansInfantMaleMiddle AgedRetrospective StudiesYoung Adultclonal hematopoiesisgenetic diagnosisimmune disordersMosaicism

Identifiers

PMID41724404
PMCPMC13087911

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.