Ultra-rare severe kidney dysplasia mimicking salt-wasting tubulopathy associated with TFCP2L1 gene variants

Area of Science:

• Pediatric Nephrology
• Medical Genetics
• Molecular Biology

Background:

• Rare monogenic diseases are a growing cause of pediatric chronic kidney disease.
• Prenatal onset Bartter syndrome is characterized by severe kidney dysfunction and salt-wasting.

Purpose of the Study:

• To identify the genetic cause of severe kidney dysfunction and salt-wasting in a preterm infant.
• To investigate the role of the TFCP2L1 gene in kidney development and homeostasis.

Main Methods:

• Clinical case description of a preterm infant with advanced kidney dysfunction.
• Genetic analysis to identify pathogenic variants.
• Phenotypic correlation with gene function.

Main Results:

• A homozygous pathogenic variant in the TFCP2L1 gene was identified.
• The patient presented with severe polyuria, electrolyte imbalances, metabolic alkalosis, and hyperuricemia.
• This case adds to the limited evidence linking TFCP2L1 variants to monogenic kidney disorders.

Conclusions:

• TFCP2L1 pathogenic variants are a cause of monogenic kidney disorders, potentially presenting as phenocopies of primary tubulopathies.
• Genetic diagnosis is crucial for managing children with refractory kidney disease and for family counseling.
• Early genetic identification facilitates targeted management and improves patient outcomes.