Williams-Beuren syndrome (WBS), due to a contiguous gene deletion of approximately 1.5 Mb at 7q11.23, is a complex developmental disorder with multisystemic manifestations including supravalvular aortic stenosis (SVAS) and a specific cognitive phenotype. Large repeats containing genes and pseudogenes flank the deletion breakpoints, and the mutation mechanism commonly appears to be unequal meiotic crossover. Except for elastin, hemizygosity of which is associated with supravalvular aortic stenosis, it is unknown which of the 18 genes in the deletion area contributes to the phenotype. Here, we report the identification and characterization of two novel genes, WBSCR20 and WBSCR22, which map to the common WBS deletion region. WBSCR22 encodes a putative methyltransferase protein strongly expressed in heart, skeletal muscle and kidney. WBSCR20 encodes a novel protein expressed in skeletal muscle with similarity to p120 (NOL1), a 120-kDa proliferation-associated nucleolar antigen, a member of an evolutionarily conserved protein family. A highly similar putative gene, WBSCR20B, flanks the WBS deletion at the telomeric side. Hemizygous deletion of either of the novel genes might contribute to the growth retardation, the myopathy or the premature aging effects in the pathogenesis of WBS.
Copyright 2002 S. Karger AG, Basel