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Molecular Genetics and Interferon Signature in the Italian Aicardi Goutières Syndrome Cohort: Report of 12 New Cases and Literature Review

Aicardi-Goutières syndrome (AGS) is a genetically determined early onset encephalopathy characterized by cerebral calcification, leukodystrophy, and increased expression of interferon-stimulated genes (ISGs). Up to now, seven genes (TREX1, RNASEH2B, RNASEH2C, RNASEH2A, ADAR1, SAMHD1, IFIH1) have bee...

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Autores principales: Garau, Jessica, Cavallera, Vanessa, Valente, Marialuisa, Tonduti, Davide, Sproviero, Daisy, Zucca, Susanna, Battaglia, Domenica, Battini, Roberta, Bertini, Enrico, Cappanera, Silvia, Chiapparini, Luisa, Crasà, Camilla, Crichiutti, Giovanni, Giustina, Elvio Dalla, D’Arrigo, Stefano, Giorgis, Valentina De, Simone, Micaela De, Galli, Jessica, Piana, Roberta La, Messana, Tullio, Moroni, Isabella, Nardocci, Nardo, Panteghini, Celeste, Parazzini, Cecilia, Pichiecchio, Anna, Pini, Antonella, Ricci, Federica, Saletti, Veronica, Salvatici, Elisabetta, Santorelli, Filippo M., Sartori, Stefano, Tinelli, Francesca, Uggetti, Carla, Veneselli, Edvige, Zorzi, Giovanna, Garavaglia, Barbara, Fazzi, Elisa, Orcesi, Simona, Cereda, Cristina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6572054/
https://www.ncbi.nlm.nih.gov/pubmed/31130681
http://dx.doi.org/10.3390/jcm8050750
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author Garau, Jessica
Cavallera, Vanessa
Valente, Marialuisa
Tonduti, Davide
Sproviero, Daisy
Zucca, Susanna
Battaglia, Domenica
Battini, Roberta
Bertini, Enrico
Cappanera, Silvia
Chiapparini, Luisa
Crasà, Camilla
Crichiutti, Giovanni
Giustina, Elvio Dalla
D’Arrigo, Stefano
Giorgis, Valentina De
Simone, Micaela De
Galli, Jessica
Piana, Roberta La
Messana, Tullio
Moroni, Isabella
Nardocci, Nardo
Panteghini, Celeste
Parazzini, Cecilia
Pichiecchio, Anna
Pini, Antonella
Ricci, Federica
Saletti, Veronica
Salvatici, Elisabetta
Santorelli, Filippo M.
Sartori, Stefano
Tinelli, Francesca
Uggetti, Carla
Veneselli, Edvige
Zorzi, Giovanna
Garavaglia, Barbara
Fazzi, Elisa
Orcesi, Simona
Cereda, Cristina
author_facet Garau, Jessica
Cavallera, Vanessa
Valente, Marialuisa
Tonduti, Davide
Sproviero, Daisy
Zucca, Susanna
Battaglia, Domenica
Battini, Roberta
Bertini, Enrico
Cappanera, Silvia
Chiapparini, Luisa
Crasà, Camilla
Crichiutti, Giovanni
Giustina, Elvio Dalla
D’Arrigo, Stefano
Giorgis, Valentina De
Simone, Micaela De
Galli, Jessica
Piana, Roberta La
Messana, Tullio
Moroni, Isabella
Nardocci, Nardo
Panteghini, Celeste
Parazzini, Cecilia
Pichiecchio, Anna
Pini, Antonella
Ricci, Federica
Saletti, Veronica
Salvatici, Elisabetta
Santorelli, Filippo M.
Sartori, Stefano
Tinelli, Francesca
Uggetti, Carla
Veneselli, Edvige
Zorzi, Giovanna
Garavaglia, Barbara
Fazzi, Elisa
Orcesi, Simona
Cereda, Cristina
author_sort Garau, Jessica
collection PubMed
description Aicardi-Goutières syndrome (AGS) is a genetically determined early onset encephalopathy characterized by cerebral calcification, leukodystrophy, and increased expression of interferon-stimulated genes (ISGs). Up to now, seven genes (TREX1, RNASEH2B, RNASEH2C, RNASEH2A, ADAR1, SAMHD1, IFIH1) have been associated with an AGS phenotype. Next Generation Sequencing (NGS) analysis was performed on 51 AGS patients and interferon signature (IS) was investigated in 18 AGS patients and 31 healthy controls. NGS identified mutations in 48 of 51 subjects, with three patients demonstrating a typical AGS phenotype but not carrying mutations in known AGS-related genes. Five mutations, in RNASEH2B, SAMHD1 and IFIH1 gene, were not previously reported. Eleven patients were positive and seven negatives for the upregulation of interferon signaling (IS > 2.216). This work presents, for the first time, the genetic data of an Italian cohort of AGS patients, with a higher percentage of mutations in RNASEH2B and a lower frequency of mutations in TREX1 than those seen in international series. RNASEH2B mutated patients showed a prevalence of negative IS consistent with data reported in the literature. We also identified five novel pathogenic mutations that warrant further functional investigation. Exome/genome sequencing will be performed in future studies in patients without a mutation in AGS-related genes.
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spelling pubmed-65720542019-06-18 Molecular Genetics and Interferon Signature in the Italian Aicardi Goutières Syndrome Cohort: Report of 12 New Cases and Literature Review Garau, Jessica Cavallera, Vanessa Valente, Marialuisa Tonduti, Davide Sproviero, Daisy Zucca, Susanna Battaglia, Domenica Battini, Roberta Bertini, Enrico Cappanera, Silvia Chiapparini, Luisa Crasà, Camilla Crichiutti, Giovanni Giustina, Elvio Dalla D’Arrigo, Stefano Giorgis, Valentina De Simone, Micaela De Galli, Jessica Piana, Roberta La Messana, Tullio Moroni, Isabella Nardocci, Nardo Panteghini, Celeste Parazzini, Cecilia Pichiecchio, Anna Pini, Antonella Ricci, Federica Saletti, Veronica Salvatici, Elisabetta Santorelli, Filippo M. Sartori, Stefano Tinelli, Francesca Uggetti, Carla Veneselli, Edvige Zorzi, Giovanna Garavaglia, Barbara Fazzi, Elisa Orcesi, Simona Cereda, Cristina J Clin Med Article Aicardi-Goutières syndrome (AGS) is a genetically determined early onset encephalopathy characterized by cerebral calcification, leukodystrophy, and increased expression of interferon-stimulated genes (ISGs). Up to now, seven genes (TREX1, RNASEH2B, RNASEH2C, RNASEH2A, ADAR1, SAMHD1, IFIH1) have been associated with an AGS phenotype. Next Generation Sequencing (NGS) analysis was performed on 51 AGS patients and interferon signature (IS) was investigated in 18 AGS patients and 31 healthy controls. NGS identified mutations in 48 of 51 subjects, with three patients demonstrating a typical AGS phenotype but not carrying mutations in known AGS-related genes. Five mutations, in RNASEH2B, SAMHD1 and IFIH1 gene, were not previously reported. Eleven patients were positive and seven negatives for the upregulation of interferon signaling (IS > 2.216). This work presents, for the first time, the genetic data of an Italian cohort of AGS patients, with a higher percentage of mutations in RNASEH2B and a lower frequency of mutations in TREX1 than those seen in international series. RNASEH2B mutated patients showed a prevalence of negative IS consistent with data reported in the literature. We also identified five novel pathogenic mutations that warrant further functional investigation. Exome/genome sequencing will be performed in future studies in patients without a mutation in AGS-related genes. MDPI 2019-05-26 /pmc/articles/PMC6572054/ /pubmed/31130681 http://dx.doi.org/10.3390/jcm8050750 Text en © 2019 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
Garau, Jessica
Cavallera, Vanessa
Valente, Marialuisa
Tonduti, Davide
Sproviero, Daisy
Zucca, Susanna
Battaglia, Domenica
Battini, Roberta
Bertini, Enrico
Cappanera, Silvia
Chiapparini, Luisa
Crasà, Camilla
Crichiutti, Giovanni
Giustina, Elvio Dalla
D’Arrigo, Stefano
Giorgis, Valentina De
Simone, Micaela De
Galli, Jessica
Piana, Roberta La
Messana, Tullio
Moroni, Isabella
Nardocci, Nardo
Panteghini, Celeste
Parazzini, Cecilia
Pichiecchio, Anna
Pini, Antonella
Ricci, Federica
Saletti, Veronica
Salvatici, Elisabetta
Santorelli, Filippo M.
Sartori, Stefano
Tinelli, Francesca
Uggetti, Carla
Veneselli, Edvige
Zorzi, Giovanna
Garavaglia, Barbara
Fazzi, Elisa
Orcesi, Simona
Cereda, Cristina
Molecular Genetics and Interferon Signature in the Italian Aicardi Goutières Syndrome Cohort: Report of 12 New Cases and Literature Review
title Molecular Genetics and Interferon Signature in the Italian Aicardi Goutières Syndrome Cohort: Report of 12 New Cases and Literature Review
title_full Molecular Genetics and Interferon Signature in the Italian Aicardi Goutières Syndrome Cohort: Report of 12 New Cases and Literature Review
title_fullStr Molecular Genetics and Interferon Signature in the Italian Aicardi Goutières Syndrome Cohort: Report of 12 New Cases and Literature Review
title_full_unstemmed Molecular Genetics and Interferon Signature in the Italian Aicardi Goutières Syndrome Cohort: Report of 12 New Cases and Literature Review
title_short Molecular Genetics and Interferon Signature in the Italian Aicardi Goutières Syndrome Cohort: Report of 12 New Cases and Literature Review
title_sort molecular genetics and interferon signature in the italian aicardi goutières syndrome cohort: report of 12 new cases and literature review
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6572054/
https://www.ncbi.nlm.nih.gov/pubmed/31130681
http://dx.doi.org/10.3390/jcm8050750
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