Screening of functional and positional candidate genes in families with common variable immunodeficiency

Background: Common variable immunodeficiency (CVID) comprises a heterogeneous group of primary antibody deficiencies with complex clinical and immunological phenotypes. The recent discovery that some CVID patients show monogenic defects in the genes encoding ICOS, TACI or CD19 prompted us to investigate several functional candidate genes in individuals with CVID. Results: The exonic, protein coding regions of the genes encoding: APRIL, BCMA, IL10, IL10R alpha, IL10R beta, IL21, IL21R, and CCL18, were analyzed primarily in familial CVID cases, who showed evidence of genetic linkage to the respective candidate gene loci and CVID families with a recessive pattern of inheritance. Two novel SNPs were identified in exon 5 and exon 8 of the IL21R gene, which segregated with the disease phenotype in one CVID family. Eleven additional SNPs in the genes encoding BCMA, APRIL, IL10, IL10Ra, IL21 and IL21R were observed at similar frequencies as in healthy donors. Conclusion: We were unable to identify obvious disease causing mutations in the protein coding regions of the analyzed genes in the studied cohort.