DNA allelic alterations within VNTR loci of scleroderma families

We have characterized genetic alterations at the molecular level in 49 scleroderma and 45 control families using variable number tandem repeats (VNTRs). Additionally, paired fibroblast cell lines from the 'affected' and 'unaffected' skin and peripheral blood leucocytes of 30 patients were also examined. All families in this study were typed for Class I Cw alleles and Class II-DRB, -DQA and -DQB to confirm family membership. There were significant rises in the level of VNTR mutations in scleroderma patients (36.7%, n = 18), their siblings (16.3%, n = 13) and offspring (21.7%, n = 15). The level of VNTR mutations in the control group was 0.6% (n = 5). These mutations did not correlate with the presence of autoantibodies and no patient was taking a known clastogenic drug. The most common VNTR site for mutation was pYNZ22 (17p13.4). Differences were also seen in the VNTR alleles between fibroblast and lymphocyte DNA from the same patient, as measured by size alteration of one of the alleles. We have found that VNTRs are unstable in scleroderma patients, relatives and offspring. The reason for the genomic changes remains unknown, but previous studies have implicated the presence of a clastogen.