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Linkage of autosomal dominant common variable immunodeficiency to chromosome 5p and evidence for locus heterogeneity

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Abstract

Common variable immunodeficiency (CVID, OMIM 240500) and selective immunoglobulin A deficiency (IgAD) are the most frequent primary immunodeficiencies in humans. Of the cases with CVID/IgAD, 20%–25% are familial, but the only previous claims of linkage or association are to the HLA region on chromosome 6p. We report the results of a genome-wide scan in three multiplex families with CVID, IgAD, and dysgammaglobulinemia, where affection is inherited in an autosomal dominant pattern. Two of the families are consistent with linkage to the telomeric region of chromosome 5p, whereas the third is consistent with linkage to the HLA region. Using a locus heterogeneity model and a conservative penetrance model, we obtained a LOD score of 3.35 for the 5p region. We sequenced the exons of one promising candidate gene within this region (PDCD6, also known as ALG-2) but found no causative mutation.

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Acknowledgements

We thank the families and their physicians for their participation in this research study, which was supported by grant GR1617/3, SFB 620 from the Deutsche Forschungsgemeinschaft and EU-Project QLRT-2001–01536 (IMPAD).

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Authors and Affiliations

  1. Division of Rheumatology and Clinical Immunology, Medical School, University of Freiburg, Hugstetterstraße 55, 79106 , Freiburg, Germany

    D. U. Braig, E. Glocker, U. Salzer, K. Warnatz, H. H. Peter & B. Grimbacher

  2. Computational Biology Branch, National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Department of Health and Human Services, Bethesda, Md., USA

    A. A. Schäffer

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  1. D. U. Braig
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  2. A. A. Schäffer
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  3. E. Glocker
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  4. U. Salzer
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  6. H. H. Peter
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  7. B. Grimbacher
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Correspondence to B. Grimbacher.

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Braig, D.U., Schäffer, A.A., Glocker, E. et al. Linkage of autosomal dominant common variable immunodeficiency to chromosome 5p and evidence for locus heterogeneity. Hum Genet 112, 369–378 (2003). https://doi.org/10.1007/s00439-002-0890-4

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