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J Clin Immunol. 2015 Oct;35(7):610-4. doi: 10.1007/s10875-015-0202-0. Epub 2015 Sep 26.

Late-Onset Combined Immunodeficiency with a Novel IL2RG Mutation and Probable Revertant Somatic Mosaicism.

Author information

1
Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
2
Department of Pediatrics, Graduate School of Medicine, University of Toyama, Toyama, Japan.
3
Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
4
Department of Pediatrics, School of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan.
5
Department of Pathology, Japanese Red Cross Nagoya first Hospital, Nagoya, Japan.
6
Department of Pediatrics, National Defense Medical College, Saitama, Japan.
7
Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
8
Department of Pediatrics, Aichi Medical University School of Medicine, Nagakute, Japan.
9
Laboratory of Sequence Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
10
Department of Pediatrics, Graduate School of Medicine, University of Toyama, Toyama, Japan. hkanegane.ped@tmd.ac.jp.
11
Department of Pediatrics and Developmental Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan. hkanegane.ped@tmd.ac.jp.

Abstract

Primary immunodeficiency disease (PID) is caused by mutations of more than two hundred immunity-related genes. In addition to the heterogeneity of the diseases, the atypical presentation of each disease caused by hypomorphic mutations or somatic mosaicism makes genetic diagnosis challenging. Next-generation sequencing tests all genes simultaneously and has proven its innovative efficacy in genomics. We describe a male PID patient without any family history of immunodeficiency. This patient suffered from recurrent infections from 1 year of age. Laboratory analysis showed hypogammaglobulinemia. T, B, and NK cells were present, but the T cell proliferative response decreased. Whole-exome sequencing analysis identified an IL2RG p.P58T missense mutation. CD8(+) and CD56(+) cells showed revertant somatic mosaicism to the wild-type allele. A late-onset and atypical presentation of the X-linked severe combined immunodeficiency (X-SCID) phenotype might be associated with revertant somatic mosaicism in T and NK cells. This patient is the seventh reported case of X-SCID with revertant somatic mosaicism. His classical clinical management did not result in a molecular diagnosis because of the atypical presentation. The coverage that is provided by whole-exome sequencing of most PID genes effectively excluded differential diagnoses other than X-SCID. As next-generation sequencing becomes available in clinical practice, it will enhance our knowledge of PID and rescue currently undiagnosed patients.

KEYWORDS:

Combined immunodeficiency; Revertant somatic mosaicism; Whole-exome sequencing; X-linked severe combined immunodeficiency

PMID:
26407811
DOI:
10.1007/s10875-015-0202-0
[Indexed for MEDLINE]

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