Mutations in the facilitative glucose transporter GLUT10 alter angiogenesis and cause arterial tortuosity syndrome

Paul J Coucke, Andy Willaert, Marja W Wessels, Bert Callewaert, Nicoletta Zoppi, Julie De Backer, Joyce E Fox, Grazia M S Mancini, Marios Kambouris, Rita Gardella, Fabio Facchetti, Patrick J Willems, Ramses Forsyth, Harry C Dietz, Sergio Barlati, Marina Colombi, Bart Loeys, Anne De Paepe

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266 Citations (Scopus)


Arterial tortuosity syndrome (ATS) is an autosomal recessive disorder characterized by tortuosity, elongation, stenosis and aneurysm formation in the major arteries owing to disruption of elastic fibers in the medial layer of the arterial wall. Previously, we used homozygosity mapping to map a candidate locus in a 4.1-Mb region on chromosome 20q13.1 (ref. 2). Here, we narrowed the candidate region to 1.2 Mb containing seven genes. Mutations in one of these genes, SLC2A10, encoding the facilitative glucose transporter GLUT10, were identified in six ATS families. GLUT10 deficiency is associated with upregulation of the TGFbeta pathway in the arterial wall, a finding also observed in Loeys-Dietz syndrome, in which aortic aneurysms associate with arterial tortuosity. The identification of a glucose transporter gene responsible for altered arterial morphogenesis is notable in light of the previously suggested link between GLUT10 and type 2 diabetes. Our data could provide new insight on the mechanisms causing microangiopathic changes associated with diabetes and suggest that therapeutic compounds intervening with TGFbeta signaling represent a new treatment strategy.

Original languageEnglish
Pages (from-to)452-457
Number of pages6
JournalNature Genetics
Issue number4
Publication statusPublished - Apr 2006


  • Amino Acid Sequence
  • Arteries
  • Chromosome Mapping
  • Chromosomes, Human, Pair 20
  • Female
  • Glucose Transport Proteins, Facilitative
  • Humans
  • Male
  • Molecular Sequence Data
  • Mutation
  • Neovascularization, Pathologic
  • Pedigree
  • Sequence Homology, Amino Acid
  • Vascular Diseases

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