A Homozygous RAG1 Gene Mutation in a Case of Combined Immunodeficiency: Clinical, Molecular, and Computational Analysis

Soukaina Essadssi; Ibtihal Benhsaien; Amina Bakhchane; Hicham Charoute; Houria Abdelghaffar; Ahmed Aziz Bousfiha; Abdelhamid Barakat

doi:10.1159/000510062

A Homozygous RAG1 Gene Mutation in a Case of Combined Immunodeficiency: Clinical, Molecular, and Computational Analysis

Hum Hered. 2019;84(6):272-278. doi: 10.1159/000510062. Epub 2020 Oct 19.

Authors

Soukaina Essadssi^{1

2}, Ibtihal Benhsaien³, Amina Bakhchane¹, Hicham Charoute¹, Houria Abdelghaffar², Ahmed Aziz Bousfiha³, Abdelhamid Barakat⁴

Affiliations

¹ Laboratory of Genomics and Human Genetics, Institut Pasteur du Maroc, Casablanca, Morocco.
² Laboratory of Biosciences, Integrated and Molecular Functional Exploration (LBEFIM), Faculty of Science and Technology of Mohammedia, Hassan II University of Casablanca, Casablanca, Morocco.
³ Clinical Immunology Unit, Ibn Rochd Hospital, King Hassan II University-AinChok, Casablanca, Morocco.
⁴ Laboratory of Genomics and Human Genetics, Institut Pasteur du Maroc, Casablanca, Morocco, hamid.barakat@pasteur.ma.

PMID: 33075768
DOI: 10.1159/000510062

Abstract

Background: The recombination-activating gene 1 and 2 (RAG1/RAG2) proteins are essential to initiate the V(D)J recombination process, the result is a diverse repertoire of antigen receptor genes and the establishment of the adaptive immunity. RAG1 mutations can lead to multiple forms of combined immunodeficiency.

Methods: In this report, whole exome sequencing was performed in a Moroccan child suffering from combined immunodeficiency, with T and B lymphopenia, autoimmune hemolytic anemia, and cytomegalovirus (CMV) infection.

Results: After filtering data and Sanger sequencing validation, one homozygous mutation c.2446G>A (p.Gly816Arg) was identified in the RAG1 gene.

Conclusion: This finding expands the spectrum of immunological and genetic profiles linked to RAG1 mutation, it also illustrates the necessity to consider RAG1 immunodeficiency in the presence of autoimmune hemolytic anemia and CMV infection, even assuming the immunological phenotype appears more or less normal.

Keywords: CMV infection; Combined immunodeficiency; Morocco; Mutation; RAG1; Recombinase-activating genes.