Using methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) of the 11p15 growth regulatory region, Scott et al. (2008) identified constitutional abnormalities at chromosome 11p15 in 13 (3%) of 437 individuals with sporadic Wilms tumor without features of overgrowth syndromes. ... Using methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) of the 11p15 growth regulatory region, Scott et al. (2008) identified constitutional abnormalities at chromosome 11p15 in 13 (3%) of 437 individuals with sporadic Wilms tumor without features of overgrowth syndromes. Six patients had paternal uniparental disomy of 11p15 and 6 had hypermethylation at the H19 (103280) differentially methylated region (DMR). There were 2 familial cases. In 1 family, 2 sibs had a microdeletion of the H19 DMR (103280.0002) that was inherited from the unaffected mother; 1 sib had isolated Wilms tumor and the other had features of BWS. In a second family, a mother and 2 daughters had a microinsertion in the H19 DMR (103280.0003), inherited from the unaffected grandmother. No abnormalities were detected in 220 controls. Analysis of tumor tissue showed that the level of H19 DMR hypermethylation was greater in tumor compared to lymphocytes, suggesting that the tumors developed by clonal expansion of cells harboring the 11p15 defect. There was no evidence of additional tumor-specific 11p15 abnormalities affecting the wildtype allele.