A novel X-linked mutation in IL2RG associated with early-onset inflammatory bowel disease: a case report of twin brothers

• Published in: Journal of medical case reports Vol. 17; no. 1; p. 307
• Main Authors: Rayzan, Elham, Sadeghalvad, Mona, Shahkarami, Sepideh, Zoghi, Samaneh, Aryan, Zahra, Mahdaviani, Seyed Alireza, Boztug, Kaan, Rezaei, Nima
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 18-07-2023; BioMed Central; BMC
• Subjects: Age; B cells; Case Report; Case reports; Cytokines; Cytomegalovirus; Diarrhea; Endoscopy; Epstein-Barr virus; Failure to thrive; Flow cytometry; Gene mutations; Genetic aspects; Genetic screening; Histocompatibility antigens; HLA histocompatibility antigens; IL2RG; Immune system; Immunodeficiency; Immunoglobulins; Infections; Inflammatory bowel disease; Lymphocytes; Medical research; Medical screening; Medicine, Experimental; Metronidazole; Mutation; Pantoprazole; Proteins; SCID; Transplants & implants; Twins; Viral infections; X chromosomes; Inflammatory bowel disease; Case report; IL2RG; SCID; Immunodeficiency
• DOI: 10.1186/s13256-023-04049-y
• EISSN: 1752-1947

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.
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.
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.