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

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 TGFb 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
TGFb signaling represent a new treatment strategy.