ClinVar Genomic variation as it relates to human health

In a study of 15 multiplex families with ankylosing spondylitis (106300), Rubin et al. (1992, 1994) found that 13 of 15 affected females and 46 of 49 affected males were HLA-B27 positive, as compared with 22 of 43 unaffected females and 16 of 40 unaffected males. The risk of ankylosing spondylitis for homozygotes was placed at 99.5% and for heterozygotes at 43% with a sporadic risk of 0.1%. The B27 haplotype did not consistently segregate with disease in 2 families, but both families still supported linkage to the major histocompatibility complex. Identity-by-descent analyses showed a significant departure from random segregation among affected avuncular (uncle/nephew-niece) and cousin pairs. The presence of HLA-B40 in HLA-B27 positive individuals increased the risk for disease more than 3-fold, confirming previous reports. Disease susceptibility modeling suggested an autosomal dominant pattern of inheritance with penetrance of approximately 20%. In this study, which involved families from Toronto and Newfoundland, B27 alleles were detected by hybridization with sequence-specific oligonucleotide probes after amplification of genomic DNA by PCR. Chronic synovitis occurs in about 10% of Indian patients with severe hemophilia (HEMA, 306700; HEMB, 306900). Ghosh et al. (2003) reported an association between the development of chronic synovitis in patients with hemophilia and the HLA-B27 allele. Twenty-one (64%) of 33 patients with both disorders had HLA-B27, compared to 23 (5%) of 440 with severe hemophilia without synovitis (odds ratio of 31.6). There were 3 sib pairs with hemophilia in whom only 1 sib had synovitis; all the affected sibs had the HLA-B27 allele, whereas the unaffected sibs did not. Chronic synovitis presented as swelling of the joint with heat and redness and absence of response to treatment with factor concentrate. Ghosh et al. (2003) suggested that patients with HLA-B27 may not be able to easily downregulate inflammatory mediators after bleeding in the joints, leading to chronic synovitis. (less)

In a study of 15 multiplex families with ankylosing spondylitis (106300), Rubin et al. (1992, 1994) found that 13 of 15 affected females and 46 of 49 affected males were HLA-B27 positive, as compared with 22 of 43 unaffected females and 16 of 40 unaffected males. The risk of ankylosing spondylitis for homozygotes was placed at 99.5% and for heterozygotes at 43% with a sporadic risk of 0.1%. The B27 haplotype did not consistently segregate with disease in 2 families, but both families still supported linkage to the major histocompatibility complex. Identity-by-descent analyses showed a significant departure from random segregation among affected avuncular (uncle/nephew-niece) and cousin pairs. The presence of HLA-B40 in HLA-B27 positive individuals increased the risk for disease more than 3-fold, confirming previous reports. Disease susceptibility modeling suggested an autosomal dominant pattern of inheritance with penetrance of approximately 20%. In this study, which involved families from Toronto and Newfoundland, B27 alleles were detected by hybridization with sequence-specific oligonucleotide probes after amplification of genomic DNA by PCR. Chronic synovitis occurs in about 10% of Indian patients with severe hemophilia (HEMA, 306700; HEMB, 306900). Ghosh et al. (2003) reported an association between the development of chronic synovitis in patients with hemophilia and the HLA-B27 allele. Twenty-one (64%) of 33 patients with both disorders had HLA-B27, compared to 23 (5%) of 440 with severe hemophilia without synovitis (odds ratio of 31.6). There were 3 sib pairs with hemophilia in whom only 1 sib had synovitis; all the affected sibs had the HLA-B27 allele, whereas the unaffected sibs did not. Chronic synovitis presented as swelling of the joint with heat and redness and absence of response to treatment with factor concentrate. Ghosh et al. (2003) suggested that patients with HLA-B27 may not be able to easily downregulate inflammatory mediators after bleeding in the joints, leading to chronic synovitis. (less)