Nakamura, Akikazu and Nomura, Shunsuke and Hara, Shoko and Thamamongood, Thiparpa and Maehara, Taketoshi and Nariai, Tadashi and Khairullah, Shasha and Tan, Kay Sin and Azuma, Kenko and Chida-Nagai, Ayako and Furutani, Yoshiyuki and Hori, Takahiro and Yamaguchi, Koji and Kawamata, Takakazu and Roder, Constantin and Akagawa, Hiroyuki (2024) Whole-exome sequencing reveals the genetic causes and modifiers of moyamoya syndrome. Scientific Reports, 14 (1). ISSN 2045-2322, DOI https://doi.org/10.1038/s41598-024-72043-5.
Full text not available from this repository.Abstract
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.
| Item Type: | Article |
|---|---|
| Funders: | Medical University, Mitsuhiro Amemiya and Akira Saito, StaGen Co. Ltd., Japan Society for the Promotion of Science [Grant no. 19K09537] |
| Uncontrolled Keywords: | Adenosine triphosphatases; Adolescent; Adult; Bone morphogenetic protein receptors, Type II; Child; Child, preschool; Exome sequencing; Female; Genes, Modifier; Genetic predisposition to disease; Humans; Infant; Male; Middle aged; Moyamoya disease; Mutation; Neurofibromatosis 1; Ubiquitin-protein ligases; Young adult |
| Subjects: | R Medicine |
| Divisions: | Faculty of Medicine > Medicine Department |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 28 Oct 2025 04:01 |
| Last Modified: | 28 Oct 2025 04:01 |
| URI: | http://eprints.um.edu.my/id/eprint/46387 |
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