Первичный иммунодефицит, связанный с гемизиговыми мутациями в гене мозина (MSN).

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

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.