■本研究旨在分析中国儿童WT1基因突变相关肾病的临床特征,探讨基因型与临床表型的关系。
■广州市妇女儿童医疗中心确诊病例,与2015年1月至2022年6月从PubMed和中国国家知识基础设施(CNKI)数据库中检索到的数据相结合,并整合到一个研究队列中;根据基因突变位点进行分组,临床表型,和肾脏病理类型。比较两组患者的临床特点,基因型和发病年龄之间的关系,临床表型,并对病理类型进行回顾性分析。
■该中心纳入了15名确诊儿童:7例非单纯性肾病,包括Denys-Drash综合征(DDS)和Frasier综合征(FS);8例孤立性抗类固醇肾病综合征(ISRNS);13例(86.7%)进展为终末期肾病(ESRD)。临床非单纯性肾病患者的初始血红蛋白和碳酸氢盐水平明显低于单纯性肾病患者,而血清肌酐水平高于单纯性肾病患者。研究队列中共有75例与WT1突变相关的肾病符合纳入和排除标准。该队列中最常见的WT1突变临床表现为DDS(29/75,38.7%)和ISRNS(37/75,49.3%)。对43例患者进行了肾活检,肾脏病理常见类型为局灶节段肾小球硬化(23/43,53.5%)和DMS(13/43,30.2%)。在队列中,外显子8突变组12例(16.0%),第9外显子组32例(42.6%),内含子9组中19个(25.3%),其他基因位点突变组12例(16.0%)。中国儿童WT1突变的常见位点是外显子9和内含子9。外显子8突变与三个月内发病年龄唯一相关[5/7;71.4%;调整后的标准化残差(AR)=4.2]。外显子8突变组的肾存活时间最短(P=0.003)。
■WT1突变相关肾病的分子和生物学特征决定了临床类型,病理特征,和肾脏生存时间;基因型和临床表型之间有很强的相关性。
UNASSIGNED: This study aimed to analyze the clinical characteristics of nephropathy associated with WT1 gene mutations in Chinese children and explore the relationship between genotype and clinical phenotype.
UNASSIGNED: Cases diagnosed at the Guangzhou Women and Children\'s Medical Center, were combined with those retrieved from PubMed and China National Knowledge Infrastructure (CNKI) databases from January 2015 to June 2022 and integrated into a study cohort; grouped according to gene mutation sites, clinical phenotype, and renal pathological types. The clinical characteristics between groups were compared, and the relationship between genotype and age of onset, clinical phenotype, and pathological type were retrospectively analyzed.
UNASSIGNED: The center enrolled 15 confirmed children: seven cases of non-simple nephropathy, including Denys-Drash syndrome (DDS) and Frasier syndrome (FS); eight cases of isolated steroid-resistant nephrotic syndrome (ISRNS); and 13 cases (86.7%) that progressed to end-stage renal disease (ESRD). The initial hemoglobin and bicarbonate levels of patients with clinical non-simple nephropathy were significantly lower than those with simple nephropathy, whereas the serum creatinine levels were higher than those of patients with simple nephropathy. A total of 75 cases of nephropathy associated with WT1 mutations in the study cohort met the inclusion and exclusion criteria. The most common clinical manifestations of WT1 mutations in this cohort were DDS (29/75, 38.7%) and ISRNS (37/75, 49.3%). A renal biopsy was performed in 43 patients, and the common types of renal pathology were focal segmental glomerulosclerosis (23/43, 53.5%) and DMS (13/43, 30.2%). Within the cohort, there were 12 cases (16.0%) in the exon 8 mutation group, 32 (42.6%) in the exon 9 group, 19 (25.3%) in the intron 9 group, and 12 (16.0%) in other gene site mutation groups. Common sites of WT1 mutations in Chinese children were exons 9 and intron 9. Exon 8 mutations were uniquely correlated with the age of onset within three months [5/7; 71.4%; Adjusted standardized residual (AR) = 4.2]. The renal survival time in the exon 8 mutation group was the shortest (P = 0.003).
UNASSIGNED: The molecular and biological characteristics of WT1 mutation-related nephropathy determine the clinical type, pathological features, and renal survival time of the disease; and there was a strong correlation between the genotype and clinical phenotype.