Molecular genetic analysis of Hungarian patients with the hyper-immunoglobulin M syndrome.

摘要

We have identified 9 disease-causing mutations in 18 hyper-immunoglobulin M (HIGM) syndrome patients from ten unrelated Hungarian families. CD40L mutation resulted in X-linked combined immunodeficiency in 11 patients (6 families) and AICDA mutation caused autosomal recessive HIGM characterized by B cell immunodeficiency in 5 patients (3 families). Two brothers with a genetically undefined form of HIGM and clinical manifestations of B cell deficiency were also included in this study. B cells from these two patients had defective CSR and skewed pattern of somatic hypermutation. Altogether, a novel CD40L truncation mutation (c.470 delA) and a new missense AICDA mutation (p.E58K) were identified. Carrier status was defined in 13 clinically healthy individuals allowing prenatal genetic testing that was performed in two affected families. This is the first comprehensive overview of molecular genetic features of Hungarian patients with HIGM syndrome.