Unusual phenotype in patients with a hypomorphic mutation in the DCLRE1C gene: IgG hypergammaglobulinemia with IgA and IgE deficiency

Amit Nahum; Raz Somech; George Shubinsky; Jacov Levy; Arnon Broides

doi:10.1016/j.clim.2020.108366

Unusual phenotype in patients with a hypomorphic mutation in the DCLRE1C gene: IgG hypergammaglobulinemia with IgA and IgE deficiency

Clin Immunol. 2020 Apr:213:108366. doi: 10.1016/j.clim.2020.108366. Epub 2020 Feb 21.

Authors

Amit Nahum¹, Raz Somech², George Shubinsky³, Jacov Levy⁴, Arnon Broides⁴

Affiliations

¹ Pediatrics Department A, Soroka University Medical Center, Beer-Sheva, Israel; Immunology Clinic, Soroka University Medical Center, and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel; The Primary Immunodeficiency Research Laboratory, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel. Electronic address: amitna@clalit.org.il.
² Pediatric Department A and Immunology Service, Jeffrey Modell Foundation Center, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel HaShomer, Sackler Faculty of Medicine, Tel Aviv University, Israel.
³ Flo Cytometry Unit, Hematology Institute and Laboratory, Soroka University Medical Center, Beer-Sheva, Israel; The Shraga Segal Department of Microbiology, Immunology, and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
⁴ Immunology Clinic, Soroka University Medical Center, and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.

PMID: 32092471
DOI: 10.1016/j.clim.2020.108366

Abstract

The nuclease Artemis is a enzyme for V(D)J recombination allowing for the creation of T and B lymphocytes as well as for the repair of radiation-induced DNA double strand breaks encoded by the DCLRE1C gene. Artemis-null mutations are a known cause of severe combined immunodeficiencies (SCIDs) with radiosensitivity. Hypomorphic mutations in Artemis have been reported to cause a "leaky SCID"" phenotype, typically with hypogammaglobulinemia. We present four patients, all harboring the same unique hypomorphic mutation in the DCLRE1C gene, an 8-base pair insertion (c.1299_1306dup, p.Cys436*) presenting with a relatively mild phenotype including pulmonary infectious EBV-related lymphoproliferative diseases, an autoimmune phenomenon. Non-typical findings of IgG hypergammaglobulinemia accompanied by IgA and IgE deficiency were recorded in all patients. The typical viral, fungal, and opportunistic infections were absent, and patients reached a relatively old age.

Keywords: Artemis; Atypical; Combined immunodeficiency.

Publication types

Case Reports
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Autoimmune Diseases / genetics
DNA-Binding Proteins / genetics*
Endonucleases / genetics*
Female
Humans
Hypergammaglobulinemia / genetics*
IgA Deficiency / genetics
Immunoglobulin E / deficiency
Immunoglobulin G*
Lymphoproliferative Disorders / genetics
Male
Mutation
Phenotype
Severe Combined Immunodeficiency / complications
Severe Combined Immunodeficiency / genetics*
Severe Combined Immunodeficiency / immunology*

Substances

DNA-Binding Proteins
Immunoglobulin G
Immunoglobulin E
DCLRE1C protein, human
Endonucleases