Molecular characterization of an intronic RNASEH2B variant in a patient with Aicardi-Goutières syndrome.
Aicardi-Goutières syndrome
Leukodystrophy
RNASEH2B
RNase H2
Splicing variant
Journal
European journal of medical genetics
ISSN: 1878-0849
Titre abrégé: Eur J Med Genet
Pays: Netherlands
ID NLM: 101247089
Informations de publication
Date de publication:
Apr 2023
Apr 2023
Historique:
received:
03
11
2022
revised:
12
01
2023
accepted:
10
02
2023
pubmed:
13
2
2023
medline:
8
3
2023
entrez:
12
2
2023
Statut:
ppublish
Résumé
Aicardi-Goutières syndrome (AGS) is a progressive multisystem disorder including encephalopathy with significant impacts on intellectual and physical abilities. An early diagnosis is becoming ever more crucial, as targeted therapies are emerging. A deep understanding of the molecular heterogeneity of AGS can help guide the early diagnosis and clinical management of patients, and inform recurrence risks. Here, we detail the diagnostic odyssey of a patient with an early presentation of AGS. Exome and genome sequencing detected an intronic RNASEH2B variant missed in a conventional leukodystrophy NGS gene panel. RNA studies demonstrated that a c.322-17 A > G variant affected splicing and caused 16-nucleotide intronic retention in the RNASEH2B transcript, introducing an out-of-frame early termination codon. RNASEH2B expression in the patient's blood was reduced when compared to controls. Our study highlights the pathogenicity of this intronic variant and the importance of its inclusion in variant assessment.
Identifiants
pubmed: 36775013
pii: S1769-7212(23)00037-X
doi: 10.1016/j.ejmg.2023.104731
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
104731Informations de copyright
Copyright © 2023 Elsevier Masson SAS. All rights reserved.