title: Moyamoya vasculopathy shows a genetic mutational gradient decreasing from East to West.
abstract: 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.
authors: Unit of Neurosurgery, Giannina Gaslini Institute, Genoa, Italy - rasoale@yahoo.it.
authors: Alessandro
authors: A
authors: Raso
authors: Unit of Neurosurgery, Giannina Gaslini Institute, Genoa, Italy.
authors: Roberto
authors: R
authors: Biassoni
authors: Unit of Neurosurgery, Giannina Gaslini Institute, Genoa, Italy.
authors: Samantha
authors: S
authors: Mascelli
authors: Unit of Neurosurgery, Giannina Gaslini Institute, Genoa, Italy.
authors: Paolo
authors: P
authors: Nozza
authors: Unit of Neurosurgery, Giannina Gaslini Institute, Genoa, Italy.
authors: Elisabetta
authors: E
authors: Ugolotti
authors: Unit of Neurosurgery, Giannina Gaslini Institute, Genoa, Italy.
authors: Eddi
authors: E
authors: Di Marco
authors: Unit of Neurosurgery, Giannina Gaslini Institute, Genoa, Italy.
authors: Patrizia
authors: P
authors: De Marco
authors: Unit of Neurosurgery, Giannina Gaslini Institute, Genoa, Italy.
authors: Elisa
authors: E
authors: Merello
authors: Unit of Neurosurgery, Giannina Gaslini Institute, Genoa, Italy.
authors: Armando
authors: A
authors: Cama
authors: Unit of Neurosurgery, Giannina Gaslini Institute, Genoa, Italy.
authors: Marco
authors: M
authors: Pavanello
authors: Unit of Neurosurgery, Giannina Gaslini Institute, Genoa, Italy.
authors: Valeria
authors: V
authors: Capra
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000293:Adolescent; D044466:Asian People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D009072:Moyamoya Disease / Q000208:ethnology / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: C557998:RNF213 protein, human; D044767:Ubiquitin-Protein Ligases; D000251:Adenosine Triphosphatases