WT1 MUTATIONS CONTRIBUTE TO ABNORMAL GENITAL SYSTEM-DEVELOPMENT AND HEREDITARY WILMS-TUMOR
WT1 MUTATIONS CONTRIBUTE TO ABNORMAL GENITAL SYSTEM-DEVELOPMENT AND HEREDITARY WILMS-TUMOR
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DOI：
10.1038/353431a0
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发表时间：
1991-10-03
期刊：
影响因子：
64.8
通讯作者：
HOUSMAN, DE
中科院分区：
文献类型：
--
作者：
PELLETIER, J;BRUENING, W;HOUSMAN, DE
Wilms瘤(WT)、无虹膜、泌尿生殖系统异常和智力低下形成与染色体11p13区DNA半合缺失相关的症状群(WAGR综合征)(参考文献1，2)。然而，目前还不清楚单个基因座的半合性是否会导致一种以上的表型。肾母细胞瘤的肿瘤抑制基因WT1已被鉴定为3，4：它在肾脏的肾小球、发育中的性腺脊5、睾丸的支持细胞6以及卵巢的上皮细胞和颗粒细胞中高水平表达，这表明除了肾脏外，它在生殖系统中也有发育作用。我们现在报告两个合并了WT和生殖器异常的个体的WT1基因的结构性突变，作为隐性癌基因在哺乳动物发育中作用的证据。
WILMS' tumour (WT), aniridia, genitourinary abnormalities and mental retardation form a symptom group (WAGR syndrome) associated with hemizygous deletions of DNA in chromosome band 11p13 (refs 1, 2). However, it has not been clear whether hemizygosity at a single locus contributes to more than one phenotype. The tumour suppressor gene for Wilms' tumour, WT1, has been characterized 3,4: it is expressed at high levels in the glomeruli of the kidney 5, as well as the gonadal ridge of the developing gonad 5, the Sertoli cells of the testis 6 and the epithelial and granulosa cells of the ovary 6, suggesting a developmental role in the genital system in addition to the kidney. We now report constitutional mutations within the WT1 genes of two individuals with a combination of WT and genital abnormalities as evidence of a role for a recessive oncogene in mammalian development.