Spondyloarthropathy, Susceptibility To, 2

For a phenotypic description and a discussion of genetic heterogeneity of spondyloarthropathy, see SPDA1 (106300).

Mapping

Although the human leukocyte antigen (HLA) B27 has been identified as a susceptibility factor in spondyloarthropathy (SpA) (see SPDA1), family and twin studies suggested that predisposition to the disease is not exclusively related to HLA-B27. To identify additional susceptibility loci, Miceli-Richard et al. (2004) genotyped 120 multiplex SpA families who were included in a genomewide scan. Linkage analyses on the first 65 families identified 4 candidate non-MHC regions on chromosomes 5q, 9q, 13q, and 17q, which were further explored in the remaining 55 multiplex families. Strong linkage was identified in the MHC region containing the HLA-B27 risk factor. Nonparametric multipoint linkage analyses of the whole data set yielded evidence of significant linkage to 9q31-q34, in the vicinity of marker D9S1776 (NPL = 4.87, lod = 5.15, p = 0.00002). By examining cosegregation of this haplotype with the disease status within the family, and by taking into account the HLA-B27 carrier status, Miceli-Richard et al. (2004) inferred a possible dominant model of inheritance with incomplete penetrance.