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

Nat Genet. 2006 Apr;38(4):452-7. doi: 10.1038/ng1764. Epub 2006 Mar 19.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • Glucose Transport Proteins, Facilitative
  • SLC2A10 protein, human

Associated data

  • RefSeq/NM_030777
  • RefSeq/NT_011362