An RTEL1 Mutation Links to Infantile-Onset Ulcerative Colitis and Severe Immunodeficiency

Alma Ziv, Lael Werner, Liza Konnikova, Aya Awad, Tim Jeske, Maximilian Hastreiter, Vanessa Mitsialis, Tali Stauber, Sarah Wall, Daniel Kotlarz, Christoph Klein, Scott B. Snapper, Yehuda Tzfati, Batia Weiss, Raz Somech, Dror S. Shouval*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Purpose: More than 50 different monogenic disorders causing inflammatory bowel disease (IBD) have been identified. Our goal was to characterize the clinical phenotype, genetic workup, and immunologic alterations in an Ashkenazi Jewish patient that presented during infancy with ulcerative colitis and unique clinical manifestations. Methods: Immune workup and whole-exome sequencing were performed, along with Sanger sequencing for confirmation. Next-generation sequencing of the TCRB and IgH was conducted for immune repertoire analysis. Telomere length was evaluated by in-gel hybridization assay. Mass cytometry was performed on patient’s peripheral blood mononuclear cells, and compared with control subjects and patients with UC. Results: The patient presented in infancy with failure to thrive and dysmorphic features, consistent with a diagnosis of dyskeratosis congenita and Hoyeraal-Hreidarsson syndrome. Severe ulcerative colitis manifested in the first year of life and proceeded to the development of a primary immunodeficiency, presenting as Pneumocystis jiroveci pneumonia and hypogammaglobulinemia. Genetic studies identified a deleterious homozygous C.3791G'A missense mutation in the helicase regulator of telomere elongation 1 (RTEL1), leading to short telomeres in the index patient. Immune repertoire studies showed polyclonal T and B cell receptor distribution, while mass cytometry analysis demonstrated marked immunological alterations, including a predominance of naïve T cells, paucity of B cells, and a decrease in various innate immune subsets. Conclusions: RTEL1 mutations are associated with significant alterations in immune landscape and can manifest with infantile-onset IBD. A high index of suspicion is required in Ashkenazi Jewish families where the carriage rate of the C.3791G'A variant is high.

Original languageAmerican English
Pages (from-to)1010-1019
Number of pages10
JournalJournal of Clinical Immunology
Issue number7
StatePublished - 1 Oct 2020

Bibliographical note

Publisher Copyright:
© 2020, Springer Science+Business Media, LLC, part of Springer Nature.


  • IBD
  • PID
  • RTEL1
  • Telomeres
  • UC
  • dyskeratosis congenita
  • monogenic


Dive into the research topics of 'An RTEL1 Mutation Links to Infantile-Onset Ulcerative Colitis and Severe Immunodeficiency'. Together they form a unique fingerprint.

Cite this