X-linked primary immunodeficiency associated with hemizygous mutations in the moesin (MSN) gene - Université de Rennes Accéder directement au contenu
Article Dans Une Revue Journal of Allergy and Clinical Immunology Année : 2016

X-linked primary immunodeficiency associated with hemizygous mutations in the moesin (MSN) gene

Sven Kracker
Claire Hivroz
Nada Jabado

Résumé

BACKGROUND: We investigated 7 male patients (from 5 different families) presenting with profound lymphopenia, hypogammaglobulinemia, fluctuating monocytopenia and neutropenia, a poor immune response to vaccine antigens, and increased susceptibility to bacterial and varicella zoster virus infections. OBJECTIVE: We sought to characterize the genetic defect involved in a new form of X-linked immunodeficiency. METHODS: We performed genetic analyses and an exhaustive phenotypic and functional characterization of the lymphocyte compartment. RESULTS: We observed hemizygous mutations in the moesin (MSN) gene (located on the X chromosome and coding for MSN) in all 7 patients. Six of the latter had the same missense mutation, which led to an amino acid substitution (R171W) in the MSN four-point-one, ezrin, radixin, moesin domain. The seventh patient had a nonsense mutation leading to a premature stop codon mutation (R533X). The naive T-cell counts were particularly low for age, and most CD8(+) T cells expressed the senescence marker CD57. This phenotype was associated with impaired T-cell proliferation, which was rescued by expression of wild-type MSN. MSN-deficient T cells also displayed poor chemokine receptor expression, increased adhesion molecule expression, and altered migration and adhesion capacities. CONCLUSION: Our observations establish a causal link between an ezrin-radixin-moesin protein mutation and a primary immunodeficiency that could be referred to as X-linked moesin-associated immunodeficiency.

Domaines

Génétique

Dates et versions

hal-01439360 , version 1 (18-01-2017)

Identifiants

Citer

Chantal Lagresle-Peyrou, Sonia Luce, Farid Ouchani, Tayebeh Shabi Soheili, Hanem Sadek, et al.. X-linked primary immunodeficiency associated with hemizygous mutations in the moesin (MSN) gene. Journal of Allergy and Clinical Immunology, 2016, 138 (6), pp.1681-1689.e8. ⟨10.1016/j.jaci.2016.04.032⟩. ⟨hal-01439360⟩
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