DNA recombination defects in Kuwait: Clinical, immunologic and genetic profile

Waleed Al-Herz; Michel J Massaad; Janet Chou; Luigi D Notarangelo; Raif S Geha

doi:10.1016/j.clim.2017.10.006

DNA recombination defects in Kuwait: Clinical, immunologic and genetic profile

Clin Immunol. 2018 Feb:187:68-75. doi: 10.1016/j.clim.2017.10.006. Epub 2017 Oct 16.

Authors

Waleed Al-Herz¹, Michel J Massaad², Janet Chou², Luigi D Notarangelo³, Raif S Geha²

Affiliations

¹ Department of Pediatrics, Faculty of Medicine, Kuwait University, Kuwait; Allergy & Clinical Immunology Unit, Pediatric Department, Al-Sabah Hospital, Kuwait. Electronic address: [email protected].
² Division of Immunology, Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, MA, United States.
³ Laboratory of Host Defences, DIR, NIAID, NIH, DHHS, Bethesda, MD, United States.

Abstract

Defects in DNA Recombination due to mutations in RAG1/2 or DCLRE1C result in combined immunodeficiency (CID) with a range of disease severity. We present the clinical, immunologic and molecular characteristics of 21 patients with defects in RAG1, RAG2 or DCLRE1C, who accounted for 24% of combined immune deficiency cases in the Kuwait National Primary Immunodeficiency Disorders Registry. The distribution of the patients was as follow: 8 with RAG1 deficiency, 6 with RAG2 deficiency and 7 with DCLRE1C deficiency. Nine patients presented with SCID, 6 with OS, 2 with leaky SCID and 4 with CID and granuloma and/or autoimmunity (CID-G/AI). Eight patients [(7 SCID and 1 OS) (38%)] received hematopoietic stem cell transplant (HSCT). The median age of HSCT was 11.5months and the median time from diagnosis to HSCT was 6months. Fifty percent of the transplanted patients are alive while only 23% of the untransplanted ones are alive.

Keywords: Artemis; Combined immunodeficiency; DCLRE1C; DNA recombination; Rag; SCID.

Publication types

Research Support, N.I.H., Intramural

MeSH terms

Adolescent
Anti-Bacterial Agents / therapeutic use
Autoimmune Diseases / genetics
Autoimmune Diseases / immunology*
Autoimmune Diseases / therapy
Child
Child, Preschool
DNA-Binding Proteins / genetics
Endonucleases / genetics
Female
Genetic Profile
Granuloma / genetics
Granuloma / immunology*
Granuloma / therapy
Hematopoietic Stem Cell Transplantation
Homeodomain Proteins / genetics
Humans
Immunoglobulins, Intravenous / therapeutic use
Immunologic Deficiency Syndromes / genetics
Immunologic Deficiency Syndromes / immunology
Immunologic Deficiency Syndromes / therapy
Immunologic Factors / therapeutic use
Infant
Kuwait
Male
Nuclear Proteins / genetics
Severe Combined Immunodeficiency / genetics
Severe Combined Immunodeficiency / immunology*
Severe Combined Immunodeficiency / therapy
V(D)J Recombination / genetics*

Substances

Anti-Bacterial Agents
DNA-Binding Proteins
Homeodomain Proteins
Immunoglobulins, Intravenous
Immunologic Factors
Nuclear Proteins
RAG2 protein, human
RAG-1 protein
DCLRE1C protein, human
Endonucleases