Editor—Familial Wilms tumour is rare, accounting for only 1-2% of cases, and is not usually associated with other tumour types or congenital malformation.1 The pattern of inheritance has been interpreted as a dominant predisposition to Wilms tumour with incomplete penetrance of approximately 30%. Following the isolation of the WT1 gene in 1990, it soon became clear that WT1 mutation did not account for any of the large Wilms tumour pedigrees and was found in only the minority (∼10%) of sporadic Wilms tumours. Pedigree specific differences in age at onset, incidence of bilateral tumours, and presence of metastases provided further evidence for the existence of more than one gene for familial Wilms tumour.1Recently, two familial Wilms tumour gene loci, designatedFWT1 and FWT2, have been mapped by genetic linkage analysis to 17q12-21 and 19q respectively.2 3

While a series of Wilms tumour families were being analysed for linkage to the putative FWT1 locus on 17q,2 one proband was noted to carry a tumour specific 11p13 deletion (theWT1 locus) and to suffer from genitourinary abnormalities (fig 1). Mutational analysis ofWT1 was therefore undertaken in this pedigree.

Family WILMS 5 was identified as a sib pair affected with unilateral Wilms tumour. The sister (No 301) presented at the age of 2 years with a tumour of fetal rhabdomyomatous type and remains well 12 years later. Her brother …