title: Linkage of autosomal dominant common variable immunodeficiency to chromosome 5p and evidence for locus heterogeneity.
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.
authors.affiliation: Division of Rheumatology and Clinical Immunology, Medical School, University of Freiburg, Hugstetterstrasse 55, 79106 Freiburg, Germany.
authors.forename: D U
authors.initials: DU
authors.lastname: Braig
authors.forename: A A
authors.initials: AA
authors.lastname: Schäffer
authors.forename: E
authors.initials: E
authors.lastname: Glocker
authors.forename: U
authors.initials: U
authors.lastname: Salzer
authors.forename: K
authors.initials: K
authors.lastname: Warnatz
authors.forename: H H
authors.initials: HH
authors.lastname: Peter
authors.forename: B
authors.initials: B
authors.lastname: Grimbacher
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D017074:Common Variable Immunodeficiency / Q000235:genetics*; D005260:Female; D018740:Genetic Heterogeneity; D008040:Genetic Linkage / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D011110:Polymorphism, Genetic
chemical_list: D005819:Genetic Markers