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The Wilms' tumour suppressor gene,  WT1 , is mutated in 10–15% of Wilms' tumours and encodes zinc-finger proteins with diverse cellular functions critical for nephrogenesis, genitourinary development, haematopoiesis and sex determination. Here we report that a novel alternative  WT1  transcript,  AWT1 , is co-expressed with  WT1  in renal and haematopoietic cells.  AWT1  maintains  WT1  exonic structure between exons 2 and 10, but deploys a new 5′-exon located in intron 1 of  WT1.  The  AWT1  gene predicts proteins of approximately 33 kDa, comprising all exon 5 and exon 9 splicing variants previously characterized for  WT1.  Although  WT1  is not genomically imprinted in kidney, we have previously shown monoallelic expression of a  WT1  antisense transcript ( WT1-AS ) that is consistent with genomic imprinting. Here we demonstrate that both  WT1-AS  and the novel  AWT1  transcript are imprinted in normal kidney with expression confined to the paternal allele. Wilms' tumours display biallelic  AWT1  expression, indicating relaxation of imprinting of  AWT1  in a subset of WTs. Our findings define human chromosome 11p13 as a new imprinted locus, and also suggest a possible molecular basis for the strong bias of paternal allele mutations and variable penetrance observed in syndromes with inherited  WT1  mutations.

Genomic imprinting at the WT1 gene involves a novel coding transcript ( AWT1 ) that shows deregulation in Wilms' tumours