Division of Endocrinology, The Children's Hospital of Zhejiang University School of Medicine, Hangzhou, China.
Acta Paediatr. 2011 Jul;100(7):e39-42. doi: 10.1111/j.1651-2227.2011.02167.x. Epub 2011 Feb 14.
The Wilms' Tumour gene is thought to have tumour suppressor activity and to play an important role in nephrogenesis, genitourinary development, haematopoiesis and sex determination. WT1 mutations will impair gonadal and urinary tract development and have been demonstrated to cause syndromes of WAGR, Denys-Drash and Fraiser.
To elucidate the role of constitutional mutations of WT1, in the expression of the different clinical feature, we describe a 14-year-9-month nonmosaic XY sex-reversed woman with pure gonadal dysgenesis (46, XY karyotype, completely female external genitalia, normal Mullerian ducts, absence of Wolffian ducts, streak gonads) who had right kidney removed at 7 months of age because of Wilms' tumour and was diagnosed as secondary thrombocytopenia (Plt 60-80 × 10(9) /L) since she was 4 years old. We sequenced the genomic DNA of all the 10 exons of the WT1 in which mutations may occur in proposita.
A new de novo insertion mutation in the first exon was found. A 'GCCGCCTCACTCC' is inserted between codon 138 and 139, resulting in the creation of a stop codon and a truncated protein.
The present data provide further evidence to support the role of WT1 in diverse cellular functions.
Wilms 瘤基因被认为具有肿瘤抑制活性，在肾发生、泌尿生殖系统发育、造血和性别决定中发挥重要作用。WT1 突变会损害性腺和泌尿道的发育，并已被证明会导致 WAGR、Denys-Drash 和 Fraser 综合征。
为了阐明 WT1 结构突变在不同临床表现中的作用，我们描述了一位 14 岁 9 个月的非嵌合性 XY 性反转女性，具有纯性腺发育不全（46，XY 核型，完全女性外生殖器，正常 Müller 管， Wolffian 管缺失，条纹性腺），7 个月时因 Wilms 瘤切除右肾，4 岁时被诊断为继发性血小板减少症（血小板 60-80×10（9）/L）。我们对先证者可能发生突变的 WT1 的所有 10 个外显子的基因组 DNA 进行了测序。
发现了一个新的第一外显子中的从头插入突变。一个 'GCCGCCTCACTCC' 插入到密码子 138 和 139 之间，导致产生一个终止密码子和一个截断的蛋白质。
本数据进一步证实了 WT1 在多种细胞功能中的作用。
