The Wilms tumour gene, WT1, in normal and abnormal nephrogenesis

The Wilms tumour gene, WT1, has been shown to play an important role in nor mal development Of the kidney and gonad. Constitutional mutations pre dispo se to both malformation and childhood tumours of these organs. There is a g enotype-phenotype correlation, with missense mutations producing more sever e abnormalities than complete absence of one allele. Two syndromes with ear ly-onset protein-losing nephropathy can be distinguished according to the t ype of WT1 mutation. Children with apparently isolated diffuse mesangial sc lerosis may also be WT1 mutation carriers. WT1 is not the major gene mutate d in Wilms tumour, but has given important insights into the molecular gene tics of this childhood embryonal kidney cancer. Recommendations for managem ent of children suspected of having a WT1 mutation are discussed.