Immundeficiency 50 and MSN Gene D81.4

IMD50 is a recessive, primary X-linked immunodeficiency characterized by recurrent bacterial or varicella-zoster virus (VZV) infections in early childhood.

In 6 patients from 4 unrelated families with IMD50, Lagresle-Peyrou et al (2016) identified a hemizygous missense mutation in the MSN gene (R171W; 309845.0001). Mutations in 2 families were identified by whole-exome sequencing and confirmed by Sanger sequencing. A seventh male from a fifth family carried a hemizygous truncating mutation in the MSN gene (R553X; 309845.0002). Four unaffected mothers carried the mutation in the heterozygous state. The patients' T cells showed an impaired proliferative response after activation by certain mitogens, which could be restored by expression of wild-type MSN. Furthermore, the T cells exhibited differential defects in cell migration and adhesion (Lagresle-Peyrou et al. 2016).

The affected patients ranged in age from 4 to 69 years.

Early detectable and persistent lymphopenia, fluctuating neutropenia that responded to G-CSF in 2 patients, and hypogammaglobulinemia. CD4+ and CD8+ T cells were decreased, and naïve CD45RA+ T cell numbers were low. Proliferative response of T cells and antibody formation were impaired. Patients also had low levels of circulating NK and B cells.

Bone marrow examination showed normal cell distribution, indicating a normal hematopoietic differentiation process. The patients had a thymus of normal size.

Lagresle-Peyrou et al (2016) reported on 7 men from 5 unrelated families with a primary immunodeficiency characterized by the occurrence of recurrent bacterial or VZV infections in early childhood. The bacterial infections involved the respiratory tract, urinary tract, and gastrointestinal tract. Three of the 5 patients who presented with VZV infections developed a complicated course with respiratory and skin manifestations. Apart from VZV, there was no recurrence of viral infections. Other features included eczema and recurrent molluscum infections. Except for episodic infections, all patients were in good general health with no additional manifestations, growth disturbances, developmental abnormalities, or impairment of chronic respiratory function.

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