A novel pathogenic variant c.262delA in PBX1 causing oligomeganephronia identified using whole-exome sequencing and a
Jiaxin Hu1, Huihui Yang1, Xiaowen Wang1
1Department of Nephrology, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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.
Insights
Oligomeganephronia, a rare kidney condition, was diagnosed in a child with abnormal ears. Genetic analysis identified a new PBX1 gene variant, linking it to this condition and expanding knowledge of kidney development disorders.
Area of Science:
- Nephrology
- Genetics
- Developmental Biology
Background:
- Oligomeganephronia (OMN) is a rare congenital renal hypoplasia characterized by reduced glomerular number and glomerular hypertrophy.
- It is diagnosed via renal biopsy and is more frequently reported in pediatric populations.
Approach:
- We present the case of an 8-year-old boy with recurrent proteinuria and dysmorphic ears.
- Whole-exome sequencing identified a novel pathogenic variant in the PBX1 gene.
- Functional prediction analyses and a literature review of 27 PBX1 variant cases were performed.
Key Points:
- A novel pathogenic PBX1 variant was identified in a child with OMN and abnormal ears.
- This finding represents the first report of PBX1 variants associated with OMN in pediatric patients.
- The study expands the known genotype-phenotype spectrum of congenital anomalies of the kidney and urinary tract with developmental delay (CAKUTED) linked to PBX1.
Conclusions:
- Pathogenic variants in PBX1 are associated with Oligomeganephronia in children.
- This discovery broadens the understanding of the genetic basis of congenital kidney diseases.
- Further research into PBX1's role in renal development is warranted.
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