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

Research output: Contribution to journalArticle

Abstract

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 wall1. 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 TGFβ pathway in the arterial wall, a finding also observed in Loeys-Dietz syndrome, in which aortic aneurysms associate with arterial tortuosity3. 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 diabetes4,5. Our data could provide new insight on the mechanisms causing microangiopathic changes associated with diabetes and suggest that therapeutic compounds intervening with TGFβ signaling represent a new treatment strategy.

Original languageEnglish (US)
Pages (from-to)452-457
Number of pages6
JournalNature Genetics
Volume38
Issue number4
DOIs
StatePublished - Apr 2006

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Facilitative Glucose Transport Proteins
Mutation
Loeys-Dietz Syndrome
Genes
Elastic Tissue
Aortic Aneurysm
Morphogenesis
Aneurysm
Pathologic Constriction
Up-Regulation
Arteries
Chromosomes
Arterial Tortuosity Syndrome
Therapeutics

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Coucke, P. J., Willaert, A., Wessels, M. W., Callewaert, B., Zoppi, N., De Backer, J., ... De Paepe, A. (2006). Mutations in the facilitative glucose transporter GLUT10 alter angiogenesis and cause arterial tortuosity syndrome. Nature Genetics, 38(4), 452-457. https://doi.org/10.1038/ng1764

Mutations in the facilitative glucose transporter GLUT10 alter angiogenesis and cause arterial tortuosity syndrome. / Coucke, Paul J.; Willaert, Andy; Wessels, Marja W.; Callewaert, Bert; Zoppi, Nicoletta; De Backer, Julie; Fox, Joyce E.; Mancini, Grazia M S; Kambouris, Marios; Gardella, Rita; Facchetti, Fabio; Willems, Patrick J.; Forsyth, Ramses; Dietz, Harry C; Barlati, Sergio; Colombi, Marina; Loeys, Bart; De Paepe, Anne.

In: Nature Genetics, Vol. 38, No. 4, 04.2006, p. 452-457.

Research output: Contribution to journalArticle

Coucke, PJ, Willaert, A, Wessels, MW, Callewaert, B, Zoppi, N, De Backer, J, Fox, JE, Mancini, GMS, Kambouris, M, Gardella, R, Facchetti, F, Willems, PJ, Forsyth, R, Dietz, HC, Barlati, S, Colombi, M, Loeys, B & De Paepe, A 2006, 'Mutations in the facilitative glucose transporter GLUT10 alter angiogenesis and cause arterial tortuosity syndrome', Nature Genetics, vol. 38, no. 4, pp. 452-457. https://doi.org/10.1038/ng1764
Coucke, Paul J. ; Willaert, Andy ; Wessels, Marja W. ; Callewaert, Bert ; Zoppi, Nicoletta ; De Backer, Julie ; Fox, Joyce E. ; Mancini, Grazia M S ; Kambouris, Marios ; Gardella, Rita ; Facchetti, Fabio ; Willems, Patrick J. ; Forsyth, Ramses ; Dietz, Harry C ; Barlati, Sergio ; Colombi, Marina ; Loeys, Bart ; De Paepe, Anne. / Mutations in the facilitative glucose transporter GLUT10 alter angiogenesis and cause arterial tortuosity syndrome. In: Nature Genetics. 2006 ; Vol. 38, No. 4. pp. 452-457.
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