Neurological involvement in monogenic podocytopathies
Olivia Boyer1,2, Géraldine Mollet3, Guillaume Dorval3,4
1Service de Néphrologie Pédiatrique, AP-HP, Centre de Référence de maladies rénales rares de l'enfant et de l'adulte (MARHEA), Hôpital Necker - Enfants Malades, 149 Rue de Sèvres, 75015, Paris, France. olivia.boyer@aphp.fr.
Pediatric Nephrology (Berlin, Germany)
|April 1, 2021
Summary
Genetic mutations cause hereditary nephrotic syndrome (NS) and neurological disorders. This review details neuro-renal syndromes, linking podocyte and neuron gene variants to proteinuria and neurological defects.
Area of Science:
- Nephrology
- Genetics
- Neurology
Background:
- Over 50 genes linked to monogenic steroid-resistant nephrotic syndrome (SRNS), primarily affecting podocyte proteins.
- Syndromic NS can present with neurological features, highlighting a physiological link between podocytes and neurons.
- Genetic variants in podocyte and neuronal genes cause phenotypes combining kidney disease with neurological disorders.
Purpose of the Study:
- To review genetic syndromes associating nephrotic range proteinuria with neurological involvement.
- To present the latest advances in understanding these complex neuro-renal disorders.
Main Methods:
- Literature review of genetic studies on hereditary nephrotic syndrome and neuro-renal disorders.
- Analysis of gene variants and their associated clinical phenotypes.
Main Results:
- Identified over 50 genes implicated in monogenic SRNS, with many encoding slit diaphragm and cytoskeletal proteins.
- Detailed specific syndromes: Galloway-Mowat syndrome (GAMOS), Pierson syndrome, and Charcot-Marie-Tooth-FSGS, each with distinct genetic causes and neuro-renal manifestations.
- Established links between podocyte and neuronal physiology, explaining shared genetic underpinnings.
Conclusions:
- Genetic syndromes frequently link nephrotic proteinuria and neurological deficits.
- Understanding these neuro-renal disorders requires a comprehensive approach to genetics, podocyte biology, and neurology.
- Further research into shared pathways can illuminate disease mechanisms and therapeutic targets.
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