IL2RG hypomorphic mutation: identification of a novel pathogenic mutation in exon 8 and a review of the literature

Abstract Background Atypical X-linked severe combined immunodeficiency (X-SCID) is a variant of cellular immunodeficiency due to hypomorphic mutations in the interleukin 2 receptor gamma (IL2RG) gene. Due to a leaky clinical phenotype, diagnosis and appropriate treatment are challenging in these pat...

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Main Authors:	Che Kang Lim, Hassan Abolhassani, Sofia K. Appelberg, Mikael Sundin, Lennart Hammarström
Format:	Article
Language:	English
Published:	BMC 2019-01-01
Series:	Allergy, Asthma & Clinical Immunology
Subjects:	Interleukin 2 receptor gamma Atypical severe combined immunodeficiency Hypomorphic mutations
Online Access:	http://link.springer.com/article/10.1186/s13223-018-0317-y

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spelling	doaj-72288f81d5c04dd8aa2c25b22858adc42020-11-25T02:05:44ZengBMCAllergy, Asthma & Clinical Immunology1710-14922019-01-011511810.1186/s13223-018-0317-yIL2RG hypomorphic mutation: identification of a novel pathogenic mutation in exon 8 and a review of the literatureChe Kang Lim0Hassan Abolhassani1Sofia K. Appelberg2Mikael Sundin3Lennart Hammarström4Division of Clinical Immunology and Transfusion Medicine, Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital HuddingeDivision of Clinical Immunology and Transfusion Medicine, Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital HuddingeDivision of Clinical Immunology and Transfusion Medicine, Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital HuddingeDepartment of Blood Disorders, Immunodeficiency and Stem Cell Transplantation, Astrid Lindgren Children’s HospitalDivision of Clinical Immunology and Transfusion Medicine, Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital HuddingeAbstract Background Atypical X-linked severe combined immunodeficiency (X-SCID) is a variant of cellular immunodeficiency due to hypomorphic mutations in the interleukin 2 receptor gamma (IL2RG) gene. Due to a leaky clinical phenotype, diagnosis and appropriate treatment are challenging in these patients. Case presentation We report a 16-year-old patient with a Tlow B+ NK+ cellular immunodeficiency due to a novel nonsense mutation in exon 8 (p.R328X) of the IL2RG gene. Functional impairment of the IL2RG was confirmed by IL2-Janus kinase 3-signal transducer and activator of transcription signaling pathway investigation. In addition, the characteristics of the mutations previously described in 39 patients with an atypical phenotype were reviewed and analyzed from the literature. Conclusion This is the first report of an atypical X-SCID phenotype due to an exon 8 mutation in the IL2RG gene. The variability in the phenotypic spectrum of classic X-SCID associated gene highlights the necessity of multi-disciplinary cooperation vigilance for a more accurate diagnostic workup.http://link.springer.com/article/10.1186/s13223-018-0317-yInterleukin 2 receptor gammaAtypical severe combined immunodeficiencyHypomorphic mutations
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Che Kang Lim Hassan Abolhassani Sofia K. Appelberg Mikael Sundin Lennart Hammarström
spellingShingle	Che Kang Lim Hassan Abolhassani Sofia K. Appelberg Mikael Sundin Lennart Hammarström IL2RG hypomorphic mutation: identification of a novel pathogenic mutation in exon 8 and a review of the literature Allergy, Asthma & Clinical Immunology Interleukin 2 receptor gamma Atypical severe combined immunodeficiency Hypomorphic mutations
author_facet	Che Kang Lim Hassan Abolhassani Sofia K. Appelberg Mikael Sundin Lennart Hammarström
author_sort	Che Kang Lim
title	IL2RG hypomorphic mutation: identification of a novel pathogenic mutation in exon 8 and a review of the literature
title_short	IL2RG hypomorphic mutation: identification of a novel pathogenic mutation in exon 8 and a review of the literature
title_full	IL2RG hypomorphic mutation: identification of a novel pathogenic mutation in exon 8 and a review of the literature
title_fullStr	IL2RG hypomorphic mutation: identification of a novel pathogenic mutation in exon 8 and a review of the literature
title_full_unstemmed	IL2RG hypomorphic mutation: identification of a novel pathogenic mutation in exon 8 and a review of the literature
title_sort	il2rg hypomorphic mutation: identification of a novel pathogenic mutation in exon 8 and a review of the literature
publisher	BMC
series	Allergy, Asthma & Clinical Immunology
issn	1710-1492
publishDate	2019-01-01
description	Abstract Background Atypical X-linked severe combined immunodeficiency (X-SCID) is a variant of cellular immunodeficiency due to hypomorphic mutations in the interleukin 2 receptor gamma (IL2RG) gene. Due to a leaky clinical phenotype, diagnosis and appropriate treatment are challenging in these patients. Case presentation We report a 16-year-old patient with a Tlow B+ NK+ cellular immunodeficiency due to a novel nonsense mutation in exon 8 (p.R328X) of the IL2RG gene. Functional impairment of the IL2RG was confirmed by IL2-Janus kinase 3-signal transducer and activator of transcription signaling pathway investigation. In addition, the characteristics of the mutations previously described in 39 patients with an atypical phenotype were reviewed and analyzed from the literature. Conclusion This is the first report of an atypical X-SCID phenotype due to an exon 8 mutation in the IL2RG gene. The variability in the phenotypic spectrum of classic X-SCID associated gene highlights the necessity of multi-disciplinary cooperation vigilance for a more accurate diagnostic workup.
topic	Interleukin 2 receptor gamma Atypical severe combined immunodeficiency Hypomorphic mutations
url	http://link.springer.com/article/10.1186/s13223-018-0317-y
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IL2RG hypomorphic mutation: identification of a novel pathogenic mutation in exon 8 and a review of the literature

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