WT1基因变异与Denys-Drash综合征和Frasier综合征的基因型-表型关联性分析

Genotype⁃Phenotype Correlation Analysis of WT1 Gene Variants in Denys⁃Drash Syndrome and Frasier Syndrome

目的 探讨WT1不同基因型与Denys-Drash综合征(DDS)和Frasier综合征(FS)不同表型之间的关联。方法 检索和归纳1991年1月1日至2023年10月31日期间NCBI PubMed和CNKI数据库收录的WT1基因变异患者信息,分析变异类型、发生位置和进展性肾功能损伤、泌尿生殖系统发育不全、肾母细胞瘤、性腺肿瘤等表型的关联性。结果 本研究纳入128篇文献,包含304例研究对象,检出86种WT1致病性变异。这些变异的位置分布特点为:最常见发生于外显子9(24/86,27.9%)和外显子8(23/86,26.7%);变异类型特点为:错义变异(51/86,59.3%)最常见,次常见为剪接位点变异(13/86,15.1%)。WT1基因变异导致的疾病种类特点为:DDS病例数最多(174/304,57.2%),其次为FS(83/304,27.3%);DDS主要由外显子9和外显子8上的错义变异(143/174,82.2%)导致,而FS主要由内含子9上的剪接位点变异(76/83,91.6%)导致。结论 WT1基因上外显子9和外显子8的错义变异主要导致DDS,而内含子9的剪接变异主要导致FS。对进展性肾损伤的婴幼儿及儿童应进行泌尿生殖系统的全面评估,早期明确基因诊断,以改善预后。

Objective This study aims to explore the association between different genotypes of WT1 gene variations and the phenotypes of Denys-Drash syndrome(DDS)and Frasier syndrome(FS).Methods Through searching and summarizing the case information of WT1 gene variations recorded in NCBI PubMed and CNKI databases from January 1,1991 to October 31,2023,we analyzed the association between variation types,occurrence locations,and phenotypes such as progressive renal function impairment,genitourinary developmental abnormalities,nephroblastoma,and gonadal tumors between DDS and FS Results A total of 128 articles,including 304 subjects,were included in this study,and 86 pathogenic variations of the WT1 gene were detected.The distribution characteristics of these variations were as follows:the most common occurrence was in exon 9(24/86,279%)and exon 8(23/86,267%);the most common variation type was missense mutation(51/86,593%),followed by splice site mutation(13/86,151%).The disease types caused by WT1 gene variations were as follows:DDS had the highest number of cases(174/304,572%),followed by FS(83/304,273%);DDS was mainly caused by missense mutations on exon 9 and exon 8(143/174,822%),while FS was mainly caused by splice site mutations on intron 9(76/83,916%).Conclusions The missense variants in exon 9 and exon 8 on the WT1 gene mainly resulted in DDS,while the splice variants in intron 9 mainly resulted in FS.Infants and children with progressive renal injury should undergo a comprehensive evaluation of the genitourinary system,and early genetic diagnosis should be established to improve prognosis.