Abstract:
Oligomeganephronia (OMN) is a rare congenital renal hypoplasia reported more often in children than in adults. The diagnosis of OMN relies on renal biopsy and exhibits a significant reduction in the number of glomeruli and pronounced glomerular hypertrophy. Here, we report the case of an 8-year-old boy with recurrent proteinuria and abnormal external ears. A renal biopsy revealed large and rare glomeruli. The histological findings confirmed the diagnosis of OMN. Whole-exome sequencing of the patient revealed a new pathogenic variant in PBX1 (hg19, NM_002585, c.262delA, p.Thr88Glnfs*3). The PBX1 gene encodes a transcription factor whose pathogenic variants can result in congenital renal and urinary system anomalies, with or without hearing loss, abnormal ears, and developmental retardation (CAKUTED). This is the first report to detect PBX1 pathogenic variants in children with OMN, a novel phenotype of human PBX1 pathogenic variants. We performed functional prediction analyses of deletions in the corresponding structural domains. We summarized 27 cases of PBX1 single pathogenic variants reported between 2003 and 2023 in terms of truncating and missense pathogenic variants, which can deepen our understanding of the PBX1 structural domain and expand our knowledge of the PBX1 genotype and phenotype.
摘要:
Oligomeganephronia(OMN)是一种罕见的先天性肾发育不全,在儿童中比在成人中更常见。OMN的诊断依赖于肾活检并且表现出肾小球数量的显著减少和明显的肾小球肥大。这里,我们报告了一个8岁男孩的病例,该男孩患有复发性蛋白尿和外耳异常。肾活检显示肾小球大而罕见。组织学发现证实了OMN的诊断。患者的全外显子组测序揭示了PBX1中的一种新的致病变异(hg19,NM_002585,c.262delA,p.Thr88Glnfs*3)。PBX1基因编码一种转录因子,其致病变异可导致先天性肾脏和泌尿系统异常,有或没有听力损失,耳朵异常,和发育迟缓(CAKUTED)。这是首次在OMN患儿中检测PBX1致病变异的报告,人类PBX1致病变体的新表型。我们对相应结构域中的缺失进行了功能预测分析。我们总结了2003年至2023年报告的27例PBX1单一致病变异,包括截断和错义致病变异,这可以加深我们对PBX1结构域的理解,扩大我们对PBX1基因型和表型的认识。