Next Article in Journal
Infliximab Induced a Dissociated Response of Severe Periodontal Biomarkers in Rheumatoid Arthritis Patients
Previous Article in Journal
How Gender Identity and Treatment Progress Impact Decision-Making, Psychotherapy and Aftercare Desires of Trans Persons
jcm-logo
Article Menu

Article Menu

Open AccessArticle

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

1
Department of Brain and Behavioral Sciences, University of Pavia, 27100 Pavia, Italy
2
Genomic and Post-Genomic Center, IRCCS Mondino Foundation, 27100 Pavia, Italy
3
Unit of Child and Adolescence Neurology, IRCCS Mondino Foundation, 27100 Pavia, Italy
4
Pediatric Neurology Unit, V. Buzzi Children’s Hospital, 20154 Milan, Italy
5
Child Neuropsichiatry, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, 00168 Roma, Italy
6
Department of Developmental Neuroscience, IRCCS Stella Maris Foundation, 56128 Pisa, Italy
7
Unit of Neuromuscular and Neurodegenerative Disorders, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy
8
S.O.D. Neuropsichiatria Infantile, Ospedali Riuniti "G. Salesi", 60123 Ancona, Italy
9
Neuroradiology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy
10
Clinica Pediatrica ASUIUD, 33100 Udine, Italy
11
Child Neurology Unit, IRCCS, Santa Maria Nuova Hospital, 42123 Reggio Emilia, Italy
12
Developmental Neurology Division, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy
13
Child Neurology and Psychiatry Unit, ASST Spedali Civili of Brescia, 25123 Brescia, Italy
14
Department of Clinical and Experimental Sciences, University of Brescia, 25123 Brescia, Italy
15
Department of Neuroradiology andLaboratory of Neurogenetics of Motion, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC H3A2B4, Canada
16
Child Neurology Unit, IRCCS Istituto delle Scienze Neurologiche, 40139 Bologna, Italy
17
Department of Pediatric Neuroscience, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy
18
Medical Genetics and Neurogenetics Unit, Movement Disorders Diagnostic Section, Fondazione Irccs IstitutoNeurologico Carlo Besta, 20133 Milan, Italy
19
Department of Pediatric Radiology and Neuroradiology, V. Buzzi Children’s Hospital, 20154 Milan, Italy
20
Neuroradiology Unit, IRCCS Mondino Foundation, 27100 Pavia, Italy
21
Unit of Child Neurology and Psychiatry, University Hospital Città della Salute e della Scienza, 10126 Turin, Italy
22
Clinical Department of Pediatrics San Paolo Hospital - ASST Santi Paolo Carlo, 20142 Milano, Italy
23
Molecular medicine, IRCCS Fondazione Stella Maris, 56128 Pisa, Italy
24
Paediatric Neurology and Neurophysiology Unit, Department of Women’s and Children’s Health, University Hospital of Padua, 35128 Padua, Italy
25
Neuroradiology Unit, Department of Radiology, ASST Santi Paolo e Carlo, San Carlo Borromeo Hospital, 20153 Milan, Italy
26
Child Neuropsychiatry Unit, IRCCS Giannina Gaslini Institute DINOGMI, University of Genoa, 16147 Genoa, Italy
*
Author to whom correspondence should be addressed.
Authors have equally contributed to this work.
Authors jointly supervised this work.
J. Clin. Med. 2019, 8(5), 750; https://doi.org/10.3390/jcm8050750
Received: 28 March 2019 / Revised: 4 May 2019 / Accepted: 8 May 2019 / Published: 26 May 2019
(This article belongs to the Section Molecular Diagnostics)
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. View Full-Text
Keywords: Aicardi-Goutières Syndrome; Next Generation Sequencing; Interferon signature Aicardi-Goutières Syndrome; Next Generation Sequencing; Interferon signature
Show Figures

Figure 1

MDPI and ACS Style

Garau, J.; Cavallera, V.; Valente, M.; Tonduti, D.; Sproviero, D.; Zucca, S.; Battaglia, D.; Battini, R.; Bertini, E.; Cappanera, S.; Chiapparini, L.; Crasà, C.; Crichiutti, G.; Dalla Giustina, E.; D’Arrigo, S.; De Giorgis, V.; De Simone, M.; Galli, J.; La Piana, R.; Messana, T.; Moroni, I.; Nardocci, N.; Panteghini, C.; Parazzini, C.; Pichiecchio, A.; Pini, A.; Ricci, F.; Saletti, V.; Salvatici, E.; Santorelli, F.M.; Sartori, S.; Tinelli, F.; Uggetti, C.; Veneselli, E.; Zorzi, G.; Garavaglia, B.; Fazzi, E.; Orcesi, S.; Cereda, C. Molecular Genetics and Interferon Signature in the Italian Aicardi Goutières Syndrome Cohort: Report of 12 New Cases and Literature Review. J. Clin. Med. 2019, 8, 750.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop