Severe combined immunodeficiency (SCID) presenting in childhood, with agammaglobulinemia, associated with novel compound heterozygous mutations in DCLRE1C

Mikael Sundin; Per Marits; Kim Ramme; Antonios G A Kolios; Jakob Nilsson

doi:10.1016/j.clim.2018.12.019

Severe combined immunodeficiency (SCID) presenting in childhood, with agammaglobulinemia, associated with novel compound heterozygous mutations in DCLRE1C

Clin Immunol. 2019 Mar:200:16-18. doi: 10.1016/j.clim.2018.12.019. Epub 2019 Jan 7.

Authors

Mikael Sundin¹, Per Marits², Kim Ramme¹, Antonios G A Kolios³, Jakob Nilsson⁴

Affiliations

¹ The Pediatric Hematology, Immunology and HCT Section, Astrid Lindgren Children's Hospital, Stockholm, Sweden.
² Department of Clinical Immunology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
³ Department of Clinical Immunology, University Hospital Zurich, Switzerland; Faculty of Medicine, University of Zurich, Zurich, Switzerland.
⁴ Department of Clinical Immunology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Immunology, University Hospital Zurich, Switzerland; Faculty of Medicine, University of Zurich, Zurich, Switzerland. Electronic address: [email protected].

PMID: 30630113
DOI: 10.1016/j.clim.2018.12.019

Abstract

Severe combined immunodeficiency (SCID) can be caused by deleterious mutations in DCLRE1C, leading to deficient non-homologous end joining by compromising the function of the Artemis protein. This impairs the process of V(D)J recombination of the T- and B-cell receptors and typically results in radiosensitive T^-, B^-, NK⁺ SCID presenting during the first months of life. We present a case of a 3-year-old girl with two novel compound heterozygous variants in DCLRE1C (c.58G>C and c.374A>C) that were associated with marked reduced numbers of peripheral T- and B-cells and undetectable total serum IgG. Despite the severe laboratory phenotype, the patient had a normal development, albeit failure to thrive (-2.5 to -3 SD), during her first years of life including day-care attendance at preschool for 1.5 years. After being diagnosed with pneumonia the clinical picture of SCID was recognized and the girl successfully underwent hematopoietic stem-cell transplantation.

Keywords: Agammaglobulinemia; Artemis; DCLRE1C; Severe combined immunodeficiency.

Publication types

Case Reports

MeSH terms

Agammaglobulinemia / complications
Agammaglobulinemia / genetics*
Agammaglobulinemia / immunology
Child, Preschool
DNA-Binding Proteins / genetics*
Endonucleases / genetics*
Female
Heterozygote
Humans
Mutation
Pneumonia, Pneumocystis / diagnosis
Pneumonia, Pneumocystis / etiology
Severe Combined Immunodeficiency / complications
Severe Combined Immunodeficiency / diagnosis
Severe Combined Immunodeficiency / genetics*
Severe Combined Immunodeficiency / immunology

Substances

DNA-Binding Proteins
DCLRE1C protein, human
Endonucleases