Analysis of Families with Common Variable Immunodeficiency (CVID) and IgA Deficiency Suggests Linkage of CVID to Chromosome 16q

摘要

Common variable immunodeficiency (CVID) is an antibody deficiency syndrome that often co-occurs in families with selective IgA deficiency (IgAD). Vořechovský et al. [American Journal of Human Genetics 641999, 1096-1109; Journal of Immunology 1642000, 4408–4416] ascertained and genotyped 101 multiplex IgAD families and used them to identify and fine map the IGAD1 locus on chromosome 6p. We analyzed the original genotype data in a subset of families with at least one case of CVID and present evidence of a CVID locus on chromosome 16q with autosomal dominant inheritance. The peak (model-based) LOD score for the best marker D16S518 is 2.83 at θ =0.07, and a four-marker LOD score under heterogeneity peaks at 3.00 with α =0.68. The (model-free) NPL score using the same markers peaks at the same location with a value of 3.38 (p = 0.0001).