Difference in Clinical Phenotype, Mutation Position, and Structural Change of RNF213 Rare Variants Between Pediatric and Adult Japanese Patients with Moyamoya Disease.
Genetics
Moyamoya disease
Phenotype
RNF213
Rare variant
Structural analysis
Journal
Translational stroke research
ISSN: 1868-601X
Titre abrégé: Transl Stroke Res
Pays: United States
ID NLM: 101517297
Informations de publication
Date de publication:
28 Sep 2023
28 Sep 2023
Historique:
received:
30
08
2023
accepted:
13
09
2023
revised:
08
09
2023
medline:
28
9
2023
pubmed:
28
9
2023
entrez:
28
9
2023
Statut:
aheadofprint
Résumé
It is unclear how rare RNF213 variants, other than the p.R4810K founder variant, affect the clinical phenotype or the function of RNF213 in moyamoya disease (MMD). This study included 151 Japanese patients with MMD. After performing targeted resequencing for all coding exons in RNF213, we investigated the clinical phenotype and statistically analyzed the genotype-phenotype correlation. We mapped RNF213 variants on a three-dimensional (3D) model of human RNF213 and analyzed the structural changes due to variants. The RNF213 p.R4810K homozygous variant, p.R4810K heterozygous variant, and wild type were detected in 10 (6.6%), 111 (73.5%), and 30 (19.9%) MMD patients, respectively. In addition, 15 rare variants were detected in 16 (10.6%) patients. In addition to the influence of the p.R4810K homozygous variant, the frequency of cerebral infarction at disease onset was higher in pediatric patients with other rare variants (3/6, 50.0%, P = 0.006) than in those with only the p.R4810K heterozygous variant or with no variants (2/51, 3.9%). Furthermore, on 3D modelling of RNF213, the majority of rare variants found in pediatric patients were located in the E3 module and associated with salt bridge loss, contrary to the results for adult patients. The clinical phenotype of rare RNF213 variants, mapped mutation position, and their predicted structural change differed between pediatric and adult patients with MMD. Rare RNF213 variants, in addition to the founder p.R4810K homozygous variant, can influence MMD clinical phenotypes or structural change which may contribute to the destabilization of RNF213.
Identifiants
pubmed: 37768541
doi: 10.1007/s12975-023-01194-w
pii: 10.1007/s12975-023-01194-w
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Japan Society for the Promotion of Science
ID : 19K18443
Organisme : Japan Society for the Promotion of Science
ID : 16K10740
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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