Whole-exome sequencing reveals the genetic causes and modifiers of moyamoya syndrome.
Humans
Moyamoya Disease
/ genetics
Exome Sequencing
Female
Male
Adult
Child
Adolescent
Genetic Predisposition to Disease
Middle Aged
Child, Preschool
Ubiquitin-Protein Ligases
/ genetics
Young Adult
Mutation
Adenosine Triphosphatases
/ genetics
Genes, Modifier
Bone Morphogenetic Protein Receptors, Type II
/ genetics
Infant
Neurofibromatosis 1
/ genetics
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
04 Oct 2024
04 Oct 2024
Historique:
received:
09
10
2023
accepted:
03
09
2024
medline:
5
10
2024
pubmed:
5
10
2024
entrez:
4
10
2024
Statut:
epublish
Résumé
Moyamoya vasculopathy secondary to various genetic disorders is classified as moyamoya syndrome (MMS). Recent studies indicate MMS occurs due to a combination of genetic modifiers and causative mutations for the primary genetic disorders. We performed whole-exome sequencing (WES) in 13 patients with various genetic disorders who developed MMS. WES successfully revealed the genetic diagnoses of neurofibromatosis type 1 (NF-1), Down syndrome, multisystemic smooth muscle dysfunction syndrome, Noonan syndrome, and alpha thalassemia. The previously reported modifier genes, RNF213 and MRVI1, were confirmed in the NF-1 and Down syndrome cases. Further analysis revealed rare hypomorphic variants in the causative genes of the primary disorders underlying MMS, such as Alagille syndrome and Rasopathies, conferred susceptibility to MMS. Genes involved in the development of pulmonary arterial hypertension (PAH), such as ABCC8 and BMPR2, were also identified as potential modifiers. The rare variants in the MMS and PAH genes were significantly enriched in the eight Japanese patients with MMS compared with the 104 Japanese individuals from the 1000 Genomes Project. Disease genes associated with the arterial occlusive conditions represented by those of Rasopathies and PAH may provide novel diagnostic markers and future therapeutic targets for MMS as well as moyamoya disease with an unknown cause.
Identifiants
pubmed: 39367156
doi: 10.1038/s41598-024-72043-5
pii: 10.1038/s41598-024-72043-5
doi:
Substances chimiques
RNF213 protein, human
EC 2.3.2.27
Ubiquitin-Protein Ligases
EC 2.3.2.27
Adenosine Triphosphatases
EC 3.6.1.-
BMPR2 protein, human
EC 2.7.11.30
Bone Morphogenetic Protein Receptors, Type II
EC 2.7.11.30
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
22720Subventions
Organisme : Japan Society for the Promotion of Science
ID : 19K09537
Informations de copyright
© 2024. The Author(s).
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