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Case report: ETS1 gene deletion associated with a low number of recent thymic emigrants in three patients with Jacobsen syndrome


Trachsel, Tina Elvira; Prader, Seraina; Steindl, Katharina; Pachlopnik Schmid, Jana (2022). Case report: ETS1 gene deletion associated with a low number of recent thymic emigrants in three patients with Jacobsen syndrome. Frontiers in Immunology, 13:867206.

Abstract

Jacobsen syndrome is a rare genetic disorder associated with a terminal deletion in chromosome 11. The clinical presentation is variable. Although immunodeficiency has been described in patients with Jacobsen syndrome, a clear genotype-phenotype correlation has not yet been established. Here, we report on the immunologic phenotypes of four patients with Jacobsen syndrome. All four patients showed one or more atypical immunologic features. One patient suffered from recurrent viral infections, two patients had experienced a severe bacterial infection and one had received antibiotic prophylaxis since early childhood. One patient had experienced severe, transient immune dysregulation. Hypogammaglobulinemia and low B cell counts were found in two patients, while the number of recent thymic emigrants (CD31+CD45RA+ CD4 cells) was abnormally low in three. When considering the six immune-related genes located within the affected part of chromosome 11 (<i>ETS1, TIRAP, FLI1, NFRKB, THYN1</i>, and <i>SNX19</i>), only the <i>ETS1</i> gene was found be deleted in the three patients with low numbers of recent thymic emigrants and non-switched memory B cells. Our findings support the hypothesis whereby Jacobsen syndrome is associated with a combined immunodeficiency with variable presentation. Further investigations of potential genotype-phenotype correlations are warranted and might help to personalize patient management in individuals lacking immune-related genes. In addition, we recommend immunologic follow-up for all patients with Jacobsen syndrome, as immune abnormalities may develop over time.

Keywords: ETS1; Jacobsen syndrome; genetic disorder; immunodeficiency; recent thymic emigrants.

Abstract

Jacobsen syndrome is a rare genetic disorder associated with a terminal deletion in chromosome 11. The clinical presentation is variable. Although immunodeficiency has been described in patients with Jacobsen syndrome, a clear genotype-phenotype correlation has not yet been established. Here, we report on the immunologic phenotypes of four patients with Jacobsen syndrome. All four patients showed one or more atypical immunologic features. One patient suffered from recurrent viral infections, two patients had experienced a severe bacterial infection and one had received antibiotic prophylaxis since early childhood. One patient had experienced severe, transient immune dysregulation. Hypogammaglobulinemia and low B cell counts were found in two patients, while the number of recent thymic emigrants (CD31+CD45RA+ CD4 cells) was abnormally low in three. When considering the six immune-related genes located within the affected part of chromosome 11 (<i>ETS1, TIRAP, FLI1, NFRKB, THYN1</i>, and <i>SNX19</i>), only the <i>ETS1</i> gene was found be deleted in the three patients with low numbers of recent thymic emigrants and non-switched memory B cells. Our findings support the hypothesis whereby Jacobsen syndrome is associated with a combined immunodeficiency with variable presentation. Further investigations of potential genotype-phenotype correlations are warranted and might help to personalize patient management in individuals lacking immune-related genes. In addition, we recommend immunologic follow-up for all patients with Jacobsen syndrome, as immune abnormalities may develop over time.

Keywords: ETS1; Jacobsen syndrome; genetic disorder; immunodeficiency; recent thymic emigrants.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Children's Hospital Zurich > Medical Clinic
04 Faculty of Medicine > Institute of Medical Genetics
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Uncontrolled Keywords:Jacobsen syndrome, genetic disorder, ETS1, immunodeficiency, recent thymic emigrants
Language:English
Date:21 October 2022
Deposited On:15 Nov 2022 12:35
Last Modified:27 Apr 2024 01:41
Publisher:Frontiers Research Foundation
ISSN:1664-3224
Additional Information:Data availability statement Publicly available datasets were analyzed in this study. This data can be found here: www.deciphergenomics.org, DECIPHER accession numbers: 368156, 456461, 456462, 456463.
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.3389/fimmu.2022.867206
Related URLs:https://www.deciphergenomics.org/ (Research Data)
PubMed ID:36341443
Project Information:
  • : FunderUniversity of Zurich
  • : Grant IDClinical Research Priority Program CYTIMM-Z
  • : Project TitleZurich initiative on novel cytokine-directed treatments for immune dysregulation
  • : Project Websitehttps://www.cytimmz.uzh.ch/
  • : FunderSNSF
  • : Grant ID320030_205097
  • : Project TitleHuman immune dysregulation in viral defense ( Jana Pachlopnik Schmid)
  • : Project Websitehttps://data.snf.ch/grants/grant/205097
  • Content: Published Version
  • Language: English
  • Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)
  • Content: Supplemental Material
  • Language: English
  • Content: Supplemental Material
  • Language: English