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Clinical and Functional Assessment of Digenicity in Renal Phosphate Wasting

Apart from increased fluid intake, patients with kidney stone disease (KSD) due to renal phosphate wasting require specific metaphylaxis. NaPi2a, NaPi2c, and NHERF1 regulate plasma phosphate concentration by reabsorbing phosphate in proximal kidney tubules and have been found altered in monogenic hy...

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Autores principales: Petzold, Friederike, Schönauer, Ria, Werner, Andreas, Halbritter, Jan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10180814/
https://www.ncbi.nlm.nih.gov/pubmed/37432176
http://dx.doi.org/10.3390/nu15092081
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author Petzold, Friederike
Schönauer, Ria
Werner, Andreas
Halbritter, Jan
author_facet Petzold, Friederike
Schönauer, Ria
Werner, Andreas
Halbritter, Jan
author_sort Petzold, Friederike
collection PubMed
description Apart from increased fluid intake, patients with kidney stone disease (KSD) due to renal phosphate wasting require specific metaphylaxis. NaPi2a, NaPi2c, and NHERF1 regulate plasma phosphate concentration by reabsorbing phosphate in proximal kidney tubules and have been found altered in monogenic hypophosphatemia with a risk of KSD. In this study, we aimed at assessing the combined genetic alterations impacting NaPi2a, NaPi2c, and NHERF1. Therefore, we screened our hereditary KSD registry for cases of oligo- and digenicity, conducted reverse phenotyping, and undertook functional studies. As a result, we identified three patients from two families with digenic alterations in NaPi2a, NaPi2c, and NHERF1. In family 1, the index patient, who presented with severe renal calcifications and a bone mineralization disorder, carried digenic alterations affecting both NaPi transporter 2a and 2c. Functional analysis confirmed an additive genetic effect. In family 2, the index patient presented with kidney function decline, distinct musculature-related symptoms, and intracellular ATP depletion. Genetically, this individual was found to harbor variants in both NaPi2c and NHERF1 pointing towards genetic interaction. In summary, digenicity and gene dosage are likely to impact the severity of renal phosphate wasting and should be taken into account in terms of metaphylaxis through phosphate substitution.
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spelling pubmed-101808142023-05-13 Clinical and Functional Assessment of Digenicity in Renal Phosphate Wasting Petzold, Friederike Schönauer, Ria Werner, Andreas Halbritter, Jan Nutrients Article Apart from increased fluid intake, patients with kidney stone disease (KSD) due to renal phosphate wasting require specific metaphylaxis. NaPi2a, NaPi2c, and NHERF1 regulate plasma phosphate concentration by reabsorbing phosphate in proximal kidney tubules and have been found altered in monogenic hypophosphatemia with a risk of KSD. In this study, we aimed at assessing the combined genetic alterations impacting NaPi2a, NaPi2c, and NHERF1. Therefore, we screened our hereditary KSD registry for cases of oligo- and digenicity, conducted reverse phenotyping, and undertook functional studies. As a result, we identified three patients from two families with digenic alterations in NaPi2a, NaPi2c, and NHERF1. In family 1, the index patient, who presented with severe renal calcifications and a bone mineralization disorder, carried digenic alterations affecting both NaPi transporter 2a and 2c. Functional analysis confirmed an additive genetic effect. In family 2, the index patient presented with kidney function decline, distinct musculature-related symptoms, and intracellular ATP depletion. Genetically, this individual was found to harbor variants in both NaPi2c and NHERF1 pointing towards genetic interaction. In summary, digenicity and gene dosage are likely to impact the severity of renal phosphate wasting and should be taken into account in terms of metaphylaxis through phosphate substitution. MDPI 2023-04-26 /pmc/articles/PMC10180814/ /pubmed/37432176 http://dx.doi.org/10.3390/nu15092081 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Petzold, Friederike
Schönauer, Ria
Werner, Andreas
Halbritter, Jan
Clinical and Functional Assessment of Digenicity in Renal Phosphate Wasting
title Clinical and Functional Assessment of Digenicity in Renal Phosphate Wasting
title_full Clinical and Functional Assessment of Digenicity in Renal Phosphate Wasting
title_fullStr Clinical and Functional Assessment of Digenicity in Renal Phosphate Wasting
title_full_unstemmed Clinical and Functional Assessment of Digenicity in Renal Phosphate Wasting
title_short Clinical and Functional Assessment of Digenicity in Renal Phosphate Wasting
title_sort clinical and functional assessment of digenicity in renal phosphate wasting
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10180814/
https://www.ncbi.nlm.nih.gov/pubmed/37432176
http://dx.doi.org/10.3390/nu15092081
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