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

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 <i>SMARCAL1</i>. A phenotype–genotype correlation has been attempted and variable expressivity of biallelic <i>SMARCAL1</i> variants...

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Bibliographic Details
Main Authors: Cristina Bertulli, Antonio Marzollo, Margherita Doria, Silvia Di Cesare, Claudio La Scola, Francesca Mencarelli, Andrea Pasini, Maria Carmen Affinita, Enrico Vidal, Pamela Magini, Paola Dimartino, Riccardo Masetti, Laura Greco, Patrizia Palomba, Francesca Conti, Andrea Pession
Format: Article
Language:English
Published: MDPI AG 2020-11-01
Series:International Journal of Molecular Sciences
Subjects:
congenital
hereditary
neonatal diseases and abnormalities
consanguinity
DNA methylation
immune system diseases
Online Access:https://www.mdpi.com/1422-0067/21/22/8604
Description
Summary:Schimke immuno-osseous dysplasia (SIOD) is a rare multisystemic disorder with a variable clinical expressivity caused by biallelic variants in <i>SMARCAL1</i>. A phenotype–genotype correlation has been attempted and variable expressivity of biallelic <i>SMARCAL1</i> 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 <i>SMARCAL1</i> 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 <i>SMARCAL1</i> mutations and to better characterizing the underlying immunologic disorder with critical implications for therapeutic and management strategies.
ISSN:1661-6596
1422-0067

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