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Pediatric Rheumatology
Published in: Pediatric Rheumatology 1/2019

Open Access 01-12-2019 | Systemic Lupus Erythematosus | Research article

Whole exome sequencing in childhood-onset lupus frequently detects single gene etiologies

Authors: Irit Tirosh, Shiri Spielman, Ortal Barel, Reut Ram, Tali Stauber, Gideon Paret, Marina Rubinsthein, Itai M. Pessach, Maya Gerstein, Yair Anikster, Rachel Shukrun, Adi Dagan, Katerina Adler, Ben Pode-Shakked, Alexander Volkov, Marina Perelman, Shoshana Greenberger, Raz Somech, Einat Lahav, Amar J. Majmundar, Shai Padeh, Friedhelm Hildebrandt, Asaf Vivante

Published in: Pediatric Rheumatology | Issue 1/2019

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Abstract

Background

Systemic lupus erythematosus (SLE) comprise a diverse range of clinical manifestations. To date, more than 30 single gene causes of lupus/lupus like syndromes in humans have been identified. In the clinical setting, identifying the underlying molecular diagnosis is challenging due to phenotypic and genetic heterogeneity.

Methods

We employed whole exome sequencing (WES) in patients presenting with childhood-onset lupus with severe and/or atypical presentations to identify cases that are explained by a single-gene (monogenic) cause.

Results

From January 2015 to June 2018 15 new cases of childhood-onset SLE were diagnosed in Edmond and Lily Safra Children’s Hospital. By WES we identified causative mutations in four subjects in five different genes: C1QC, SLC7A7, MAN2B1, PTEN and STAT1. No molecular diagnoses were established on clinical grounds prior to genetic testing.

Conclusions

We identified a significant fraction of monogenic SLE etiologies using WES and confirm the genetic locus heterogeneity in childhood-onset lupus. These results highlight the importance of establishing a genetic diagnosis for children with severe or atypical lupus by providing accurate and early etiology-based diagnoses and improving subsequent clinical management.
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Metadata
Title
Whole exome sequencing in childhood-onset lupus frequently detects single gene etiologies
Authors
Irit Tirosh
Shiri Spielman
Ortal Barel
Reut Ram
Tali Stauber
Gideon Paret
Marina Rubinsthein
Itai M. Pessach
Maya Gerstein
Yair Anikster
Rachel Shukrun
Adi Dagan
Katerina Adler
Ben Pode-Shakked
Alexander Volkov
Marina Perelman
Shoshana Greenberger
Raz Somech
Einat Lahav
Amar J. Majmundar
Shai Padeh
Friedhelm Hildebrandt
Asaf Vivante
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Pediatric Rheumatology / Issue 1/2019
Electronic ISSN: 1546-0096
DOI
https://doi.org/10.1186/s12969-019-0349-y

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