Moyamoya vasculopathy shows a genetic mutational gradient decreasing from East to West

Alessandro Raso, Roberto Biassoni, Samantha Mascelli, Paolo Nozza, Elisabetta Ugolotti, Eddi Di Marco, Patrizia De Marco, Elisa Merello, Armando Cama, Marco Pavanello, Valeria Capra

Research output: Contribution to journalArticlepeer-review


BACKGROUND: Moyamoya disease (MMD) is a chronic, occlusive cerebrovascular disease characterized by bilateral steno-occlusive changes at the terminal portion of the internal carotid arteries and an abnormal vascular network at the base of the brain determining stroke in children. Patients with a similar vasculopathy and associated conditions are affected by the moyamoya syndrome (MMS). Most of the studies focused on MMD were carried out on East-Asian population. Ring Finger 213 (RNF213) has been identified as the strongest susceptibility gene for MMD in East-Asian people. Overall, 74.5% of the East-Asian patients carry the founder variant p.Arg4810Lys of RNF213 never reported in Caucasians. A different genetic landscape among the diverse ethnic populations seems to exist.

METHODS: We sequenced the coding sequence region of RNF213, TGFB1 and PDGFRB in 21 ethnically homogeneous Italian children with moyamoya; comprehensive sequencing data are available from parents of eight of them. The analyses were carried out by NGS on Thermo-fisher PGM platform. We also performed a comprehensive review of the literature about the variations of these three genes in Caucasian patients.

RESULTS: Several new variants of RNF213 gene were detected, in particular, two new pathogenic mutations on RNF213 (p.Trp4677Leu and p.Cys4017Ser) were identified in one MMS case and in one MMD case, respectively. Moreover, in a MMS case a new probably causing disease mutation p.Pro1063Thr of PDGFRB was detected.

CONCLUSIONS: The genetic susceptibility of Asian moyamoya vasculopathy seems to differ from the Caucasian disease. No additional differences seem to exist between MMD and MMS.

Original languageEnglish
Pages (from-to)165-172
Number of pages8
JournalJ. Neurosurg. Sci.
Issue number2
Publication statusPublished - Apr 2020


  • Adenosine Triphosphatases/genetics
  • Adolescent
  • Asian Continental Ancestry Group/genetics
  • Child
  • Child, Preschool
  • Female
  • Genetic Predisposition to Disease/genetics
  • Humans
  • Male
  • Moyamoya Disease/ethnology
  • Mutation/genetics
  • Ubiquitin-Protein Ligases/genetics


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