一名中国女孩的 Denys-Drash 综合征中存在 WT1 基因突变。
A novel WT1 gene mutation in a chinese girl with denys-drash syndrome.
机构信息
Department of Surgical Oncology, Children's Hospital, National Clinical Research Center for Child Health, Zhejiang University School of Medicine, Hangzhou, China.
Department of Pathology, Children's Hospital, National Clinical Research Center for Child Health, Zhejiang University School of Medicine, Hangzhou, China.
出版信息
J Clin Lab Anal. 2021 May;35(5):e23769. doi: 10.1002/jcla.23769. Epub 2021 May 4.
OBJECTIVE
Denys-Drash syndrome (DDS) is defined by the triad of Wilms tumor, nephrotic syndrome, and/or ambiguous genitalia. Genetic testing may help identify new gene mutation sites and play an important role in clinical decision-making.
METHODS
We present a patient with an XY karyotype and female appearance, nephropathy, and Wilms tumor in the right kidney. Genomic DNA was extracted from peripheral blood cells according to standard protocols. "Next-generation" sequencing (NGS) was performed to identify novel variants. The variant was analyzed with Mutation Taster, and its function was explored by a cell growth inhibition assay.
RESULTS
We found the first case of Denys-Drash syndrome with the uncommon missense mutation (c.1420C>T, p.His474 Tyr) in the WT1 gene. In silico analysis, the variant was predicted "disease-causing" by Mutation Taster. The mutated variant showed a weaker effect in inhibiting tumor cells than wild-type WT1.
CONCLUSIONS
The uncommon missense mutation (c.1420C>T, p.His474 Tyr) in the WT1 gene may be a crucial marker in DDS.
目的
Denys-Drash 综合征（DDS）的定义为三联征，包括Wilms 瘤、肾病综合征和/或生殖器模糊。基因检测有助于识别新的基因突变位点，并在临床决策中发挥重要作用。
方法
我们报告了一例具有 XY 核型和女性外观、肾病和右肾 Wilms 瘤的患者。根据标准方案从外周血淋巴细胞中提取基因组 DNA。采用“下一代”测序（NGS）鉴定新的变异。通过 Mutation Taster 对变异进行分析，并通过细胞生长抑制试验探索其功能。
结果
我们发现首例 WT1 基因中罕见错义突变（c.1420C>T，p.His474Tyr）的 Denys-Drash 综合征。通过 Mutation Taster 预测该变异为“致病变异”。与野生型 WT1 相比，突变型变体在抑制肿瘤细胞方面的作用较弱。
结论
WT1 基因中的罕见错义突变（c.1420C>T，p.His474Tyr）可能是 DDS 的重要标志物。
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