Tehran University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share this content! On (X network) By
A Novel X-Linked Mutation in Il2rg Associated With Early-Onset Inflammatory Bowel Disease: A Case Report of Twin Brothers Publisher Pubmed



Rayzan E1, 2 ; Sadeghalvad M2, 3 ; Shahkarami S4, 5 ; Zoghi S6 ; Aryan Z7 ; Mahdaviani SA8 ; Boztug K9 ; Rezaei N2, 3
Authors
Show Affiliations
Authors Affiliations
  1. 1. International Hematology/Oncology of Pediatrics’ Experts (IHOPE), Universal Scientific Education and Research Network (USERN), Boston, MA, United States
  2. 2. Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children’s Medical Center Hospital, Tehran University of Medical Science, Dr Qarib St, Keshavarz Blvd, Tehran, 14194, Iran
  3. 3. Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Dr. Von Hauner Children’s Hospital, Ludwig-Maximilians-University Munich, Munich, Germany
  5. 5. Medical Genetics Network (MeGeNe), Universal Scientific Education and Research Network (USERN), Munich, Germany
  6. 6. Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, Vienna, Austria
  7. 7. Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, United States
  8. 8. Pediatric Respiratory Disease Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
  9. 9. Department of Pediatric Hematology and Oncology, St. Anna Children’s Hospital, Department of Pediatrics, Medical University of Vienna, Vienna, Austria

Source: Journal of Medical Case Reports Published:2023


Abstract

Background: X-linked severe combined immunodeficiency is caused by IL2RG gene mutation. Several variations have been identified in the IL2RG gene, which potentially can prevent the production of nonfunctional proteins. Herein, a novel X-linked variant in the IL2RG gene is reported in twin brothers, associated with inflammatory bowel symptoms. Case presentation: The patients were 26-month-old monozygotic twin middle-eastern males with failure to thrive and several inpatient admissions due to severe chronic nonbloody diarrhea that started at the age of 12 months. Pancolitis was revealed after performing upper and lower gastrointestinal endoscopies on the twin with more severe gastrointestinal symptoms. Flow cytometric evaluation of the peripheral blood cells showed low levels of CD4+ cells in both patients. Next generation sequencing-based gene panel test results of the two patients proved a novel heterozygous missense X-linked IL2RG mutation (70330011 A > G, p.Trp197Arg) in one of the patients, which was predicted to be deleterious (CADD score of 28), which soon after was confirmed by Sanger segregation in his twin brother. Both parents were wild types and had never experienced similar symptoms. The patients received an human leukocyte antigen (HLA)-matched cord blood transplant. The twin with more severe gastrointestinal symptoms died 1 month after transplantation. In his brother, watery diarrhea eventually subsided after transplantation. Conclusion: Intestinal involvement in X-linked severe combined immunodeficiency is a rare presentation that might be neglected. The increasing availability of genetic screening tests worldwide could be helpful for early detection of such lethal primary immunodeficiency diseases and in implementing effective interventions to handle the severe outcomes. © 2023, The Author(s).
Related Docs
1. Il2rg Hypomorphic Mutation: Identification of a Novel Pathogenic Mutation in Exon 8 and a Review of the Literature, Allergy# Asthma and Clinical Immunology (2019)
2. X-Linked Scid With a Rare Mutation, Allergy# Asthma and Clinical Immunology (2021)