Immunoglobulin class switch recombination deficiencies (Ig-CSR-D) are characterized by normal or elevated serum IgM level and absence of IgG, IgA, and IgE. Most reported cases are due to X-linked CD40L deficiency. Activation-induced cytidine deaminase deficiency is the most frequent autosomal recessive form, whereas CD40 deficiency is more rare. Herein, we present the first North African study on hyper IgM (HIGM) syndrome including 16 Tunisian patients. Phenotypic and genetic studies allowed us to determine their molecular basis. Three CD40LG mutations have been identified including two novels (c.348_351dup and c.782_*2del) and one already reported mutation (g.6182G>A). No mutation has been found in another patient despite the lack of CD40L expression. Interestingly, three AICDA mutations have been identified in 11 patients. Two mutations were novel (c.91T>C and c.389A>C found in one and five patients respectively), and one previously reported splicing mutation (c.156+1T>G) was found in five patients. Only one CD40-deficient patient, bearing a novel mutation (c.109T>G), has been identified. Thus, unlike previous reports, AID deficiency is the most frequent underlying molecular basis (68%) of Ig-CSR-D in Tunisian patients. This finding and the presence of specific recurrent mutations are probably due to the critical role played by inbreeding in North African populations.
Keywords: Activation-induced cytidine deaminase; CD40; CD40LG; Class switch recombination; Consanguinity; Hyper IgM syndrome.