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Expanding Phenotype of Schimke Immuno-Osseous Dysplasia: Congenital Anomalies of the Kidneys and of the Urinary Tract and Alteration of NK Cells

Schimke immuno-osseous dysplasia (SIOD) is a rare multisystemic disorder with a variable clinical expressivity caused by biallelic variants in SMARCAL1. A phenotype–genotype correlation has been attempted and variable expressivity of biallelic SMARCAL1 variants may be associated with environmental a...

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Autores principales: Bertulli, Cristina, Marzollo, Antonio, Doria, Margherita, Di Cesare, Silvia, La Scola, Claudio, Mencarelli, Francesca, Pasini, Andrea, Affinita, Maria Carmen, Vidal, Enrico, Magini, Pamela, Dimartino, Paola, Masetti, Riccardo, Greco, Laura, Palomba, Patrizia, Conti, Francesca, Pession, Andrea
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7696905/
https://www.ncbi.nlm.nih.gov/pubmed/33203071
http://dx.doi.org/10.3390/ijms21228604
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author Bertulli, Cristina
Marzollo, Antonio
Doria, Margherita
Di Cesare, Silvia
La Scola, Claudio
Mencarelli, Francesca
Pasini, Andrea
Affinita, Maria Carmen
Vidal, Enrico
Magini, Pamela
Dimartino, Paola
Masetti, Riccardo
Greco, Laura
Palomba, Patrizia
Conti, Francesca
Pession, Andrea
author_facet Bertulli, Cristina
Marzollo, Antonio
Doria, Margherita
Di Cesare, Silvia
La Scola, Claudio
Mencarelli, Francesca
Pasini, Andrea
Affinita, Maria Carmen
Vidal, Enrico
Magini, Pamela
Dimartino, Paola
Masetti, Riccardo
Greco, Laura
Palomba, Patrizia
Conti, Francesca
Pession, Andrea
author_sort Bertulli, Cristina
collection PubMed
description Schimke immuno-osseous dysplasia (SIOD) is a rare multisystemic disorder with a variable clinical expressivity caused by biallelic variants in SMARCAL1. A phenotype–genotype correlation has been attempted and variable expressivity of biallelic SMARCAL1 variants may be associated with environmental and genetic disturbances of gene expression. We describe two siblings born from consanguineous parents with a diagnosis of SIOD revealed by whole exome sequencing (WES). Results: A homozygous missense variant in the SMARCAL1 gene (c.1682G>A; p.Arg561His) was identified in both patients. Despite carrying the same variant, the two patients showed substantial renal and immunological phenotypic differences. We describe features not previously associated with SIOD—both patients had congenital anomalies of the kidneys and of the urinary tract and one of them succumbed to a classical type congenital mesoblastic nephroma. We performed an extensive characterization of the immunophenotype showing combined immunodeficiency characterized by a profound lymphopenia, lack of thymic output, defective IL-7Rα expression, and disturbed B plasma cells differentiation and immunoglobulin production in addition to an altered NK-cell phenotype and function. Conclusions: Overall, our results contribute to extending the phenotypic spectrum of features associated with SMARCAL1 mutations and to better characterizing the underlying immunologic disorder with critical implications for therapeutic and management strategies.
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spelling pubmed-76969052020-11-29 Expanding Phenotype of Schimke Immuno-Osseous Dysplasia: Congenital Anomalies of the Kidneys and of the Urinary Tract and Alteration of NK Cells Bertulli, Cristina Marzollo, Antonio Doria, Margherita Di Cesare, Silvia La Scola, Claudio Mencarelli, Francesca Pasini, Andrea Affinita, Maria Carmen Vidal, Enrico Magini, Pamela Dimartino, Paola Masetti, Riccardo Greco, Laura Palomba, Patrizia Conti, Francesca Pession, Andrea Int J Mol Sci Article Schimke immuno-osseous dysplasia (SIOD) is a rare multisystemic disorder with a variable clinical expressivity caused by biallelic variants in SMARCAL1. A phenotype–genotype correlation has been attempted and variable expressivity of biallelic SMARCAL1 variants may be associated with environmental and genetic disturbances of gene expression. We describe two siblings born from consanguineous parents with a diagnosis of SIOD revealed by whole exome sequencing (WES). Results: A homozygous missense variant in the SMARCAL1 gene (c.1682G>A; p.Arg561His) was identified in both patients. Despite carrying the same variant, the two patients showed substantial renal and immunological phenotypic differences. We describe features not previously associated with SIOD—both patients had congenital anomalies of the kidneys and of the urinary tract and one of them succumbed to a classical type congenital mesoblastic nephroma. We performed an extensive characterization of the immunophenotype showing combined immunodeficiency characterized by a profound lymphopenia, lack of thymic output, defective IL-7Rα expression, and disturbed B plasma cells differentiation and immunoglobulin production in addition to an altered NK-cell phenotype and function. Conclusions: Overall, our results contribute to extending the phenotypic spectrum of features associated with SMARCAL1 mutations and to better characterizing the underlying immunologic disorder with critical implications for therapeutic and management strategies. MDPI 2020-11-15 /pmc/articles/PMC7696905/ /pubmed/33203071 http://dx.doi.org/10.3390/ijms21228604 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bertulli, Cristina
Marzollo, Antonio
Doria, Margherita
Di Cesare, Silvia
La Scola, Claudio
Mencarelli, Francesca
Pasini, Andrea
Affinita, Maria Carmen
Vidal, Enrico
Magini, Pamela
Dimartino, Paola
Masetti, Riccardo
Greco, Laura
Palomba, Patrizia
Conti, Francesca
Pession, Andrea
Expanding Phenotype of Schimke Immuno-Osseous Dysplasia: Congenital Anomalies of the Kidneys and of the Urinary Tract and Alteration of NK Cells
title Expanding Phenotype of Schimke Immuno-Osseous Dysplasia: Congenital Anomalies of the Kidneys and of the Urinary Tract and Alteration of NK Cells
title_full Expanding Phenotype of Schimke Immuno-Osseous Dysplasia: Congenital Anomalies of the Kidneys and of the Urinary Tract and Alteration of NK Cells
title_fullStr Expanding Phenotype of Schimke Immuno-Osseous Dysplasia: Congenital Anomalies of the Kidneys and of the Urinary Tract and Alteration of NK Cells
title_full_unstemmed Expanding Phenotype of Schimke Immuno-Osseous Dysplasia: Congenital Anomalies of the Kidneys and of the Urinary Tract and Alteration of NK Cells
title_short Expanding Phenotype of Schimke Immuno-Osseous Dysplasia: Congenital Anomalies of the Kidneys and of the Urinary Tract and Alteration of NK Cells
title_sort expanding phenotype of schimke immuno-osseous dysplasia: congenital anomalies of the kidneys and of the urinary tract and alteration of nk cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7696905/
https://www.ncbi.nlm.nih.gov/pubmed/33203071
http://dx.doi.org/10.3390/ijms21228604
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