The actin-binding moesin (MSN) protein plays an important role in membrane organization, receptor signalling, lymphocyte migration and immunological synapse formation. Mutations in the MSN gene cause an X-linked recessive inheritance disorder called immunodeficiency 50 (IMD-50) affecting the lymphocyte number, migration and adhesion. We investigated two male siblings with chronic leg ulcers and total tooth loss. Because of the identical phenotype, we looked for an immunodeficiency or genetic alteration in the background. Immunohaematological studies and whole exome sequencing (WES) were performed on the siblings and their mother. Moreover, gene expression and western blot analyses were performed in patients, their parents and healthy controls to confirm the pathogenicity of the genetic variation. In addition to the ulceration and tooth loss, immunohaematological examination revealed, that both patients have autoimmune thyroiditis, positivity for lupus anticoagulant syndrome, cryoglobulinemia and cold agglutinin diseas. Laboratory tests revealed low naive T cell, elevated activated Th cell and CD4+ T cell counts and decreased CD8+ T cells. Following the WES, bioinformatics analysis identified a hemizygous nonsense mutation within the exon 6 of MSN gene localized on the X chromosome (c.650G>A; W217X). Whereas, tissue mosaicism was described in asymptomatic mother. As we know, this MSN gene mutation has not been determined in the UCSC Genome Browser database. Western blot analysis demonstrated a lack of MSN protein in lymphocytes from the patients compared to the mother and healthy controls. Significantly decreased MSN mRNA expression was detected in the siblings compared to lymphocytes from healthy controls and the mother. The above-detailed symptoms associated with the W217X mutation may be considered a novel phenotype of IMD-50. This study highlights the utility and role of WES in the diagnosis of rare or novel forms of immunodeficiencies.

ESDRLB015 - New mutation in the moesin gene leads to a novel phenotype of immunodeficiency 50

50th Annual Meeting of the European Society for Dermatological Research. VIRTUAL MEETING