Other Zinc Finger Proteins: WTl and GLI3

Abstract Although the nuclear receptor superfamily has an impressive and steadily growing number of members, it represents only a small subset of all known zinc finger transcription factors. Among the dozens of other such factors encoded in the human genome, defects in WTl and GLI3 have been associated with human malformation syndromes and, in the case of WTl, predisposition to tumorigenesis. Germline deletions of chromosome llp13 result in the autosomal dominant WAGR syndrome (MIM 194072), which is characterized by predis position to Wilms tumor, congenital niridia, genitourinary malformations, and mental !:etardation (Riccardi et al., 1978). A contiguous gene syndrome was proposed as the basis for the pleiotropic phenotypic man ifestations (Schmickel, 1986). The predisposition to Wilms tumor (ne phroblastoma) was proposed to be caused by the presence of an inacti vating germline mutation (the llp13 deletion) that was present in all cells of the target organ (the kidney). If tumorigenesis required the in activation of both alleles of a “tumor suppressor” gene within a single cell, then the likelihood of this occurring would be greatly increased by the presence of the first “hit” within all cells of the target organ (Knud son, 1971).