Journal article
DNA-BINDING CAPACITY OF THE WT1 PROTEIN IS ABOLISHED BY DENYS-DRASH SYNDROME WT1 POINT MUTATIONS
M LITTLE, G HOLMES, W BICKMORE, V VANHEYNINGEN, N HASTIE, B WAINWRIGHT
HUMAN MOLECULAR GENETICS | OXFORD UNIV PRESS | Published : 1995
DOI: 10.1093/hmg/4.3.351
Abstract
Constitutional point mutations in the zinc finger (ZF) region of the Wilms' tumour suppressor gene 1 (WT1) lead to Denys-Drash syndrome (DDS). Patients with this syndrome display renal failure, Wilms' tumour (WT) and pseudohermaphroditism. DDS WT1 mutations fall into three major categories: (a) missense mutations altering amino acids which directly interact with the DNA target; (b) substitution of amino acids involved in zinc complexing; and (c) nonsense mutations leading to the removal of at least two zinc fingers. We have expressed the WT1 zinc fingers as glutathione-S-transferase fusion proteins, with the lysine-threonine-serine (KTS) alternate splice between ZF3 and ZF4 either present or..
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Awarded by MRC
Awarded by Medical Research Council