Chen Huanru, Zhang Miao, Lin Jinai, Lu Jieyi, Zhong Fazhan, Zhong Fu, Gao Xia, Liao Xin
Department of Nephrology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Front Pediatr. 2023 Jul 27;11:1192021. doi: 10.3389/fped.2023.1192021. eCollection 2023.
This study aimed to analyze the clinical characteristics of nephropathy associated with gene mutations in Chinese children and explore the relationship between genotype and clinical phenotype.
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.
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 mutations in the study cohort met the inclusion and exclusion criteria. The most common clinical manifestations of 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 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 ( = 0.003).
The molecular and biological characteristics of 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.
本研究旨在分析中国儿童基因突变相关肾病的临床特征，并探讨基因型与临床表型之间的关系。
将在广州妇女儿童医疗中心确诊的病例，与2015年1月至2022年6月从PubMed和中国知网（CNKI）数据库检索到的病例合并，纳入一个研究队列；根据基因突变位点、临床表型和肾脏病理类型进行分组。比较各组之间的临床特征，并回顾性分析基因型与发病年龄、临床表型和病理类型之间的关系。
该中心纳入了15例确诊儿童：7例非单纯性肾病，包括迪尼-德拉斯综合征（DDS）和弗雷泽综合征（FS）；8例孤立性激素抵抗型肾病综合征（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显著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例与突变相关的肾病病例符合纳入和排除标准。该队列中突变最常见的临床表现为DDS（29/75，38.7%）和ISRNS（37/75，49.3%）。43例患者进行了肾活检，常见的肾脏病理类型为局灶节段性肾小球硬化（23/43，53.5%）和弥漫性系膜硬化（DMS，13/43，30.2%）。在该队列中，外显子8突变组有12例（16.0%），外显子9组有32例（42.6%），内含子9组有19例（25.3%），其他基因位点突变组有12例（16.0%）。中国儿童突变的常见位点是外显子9和内含子9。外显子8突变与3个月内的发病年龄唯一相关[5/7；71.4%；校正标准化残差（AR）=4.2]。外显子8突变组的肾脏存活时间最短（=0.003）。
突变相关肾病的分子生物学特征决定了疾病的临床类型、病理特征和肾脏存活时间；基因型与临床表型之间存在很强的相关性。
