Expression of exogenous, tagged GLUT10 in fibroblasts from an ATS patient revealed a strict co-localization with the ER marker protein disulfide isomerase (PDI).
Virtual screening expands this possibility to explore more compounds that can interact with GLUT10 and may aid in understanding the mechanisms leading to ATS.
Transport of dehydroascorbic acid is impaired in the endomembranes of fibroblasts from arterial tortuosity syndrome (ATS) patients, due to the mutation in the gene coding for glucose transporter GLUT10.
Glucose transporter 10 (GLUT10) is a member of the GLUT family of membrane transporters, and mutations in this gene cause arterial tortuosity syndrome (ATS).
The present results demonstrate that GLUT10 is a DAA transporter and DAA transport is diminished in the endomembranes of fibroblasts from ATS patients.
The role of GLUT10 in ATS pathogenesis remains an enigma, and the transported metabolite(s), i.e. glucose and/or dehydroascorbic acid, have not been clearly elucidated.
Arterial Tortuosity Syndrome: homozygosity for two novel and one recurrent SLC2A10 missense mutations in three families with severe cardiopulmonary complications in infancy and a literature review.
We delineate the clinical spectrum and describe the histology in arterial tortuosity syndrome (ATS), a rare connective tissue disorder characterized by tortuosity of the large and medium-sized arteries, caused by mutations in SLC2A10.
Recent data indicate that loss-of-function mutation in the gene encoding the facilitative glucose transporter GLUT10 (SLC2A10) causes arterial tortuosity syndrome via upregulation of the TGF-β pathway in the arterial wall, a mechanism possibly causing vascular changes in diabetes.
Patients harboring a TGFBR1 mutation have similar survival rates (80% survival at 60 years), aortic risk (23% aortic dissection and 18% preventive aortic surgery), and prevalence of extra-aortic features (29% hypertelorism, 53% cervical arterial tortuosity, and 27% wide scars) when compared with patients harboring a TGFBR2 mutation.
The disease is characterized by the triad of arterial tortuosity and aneurysms, hypertelorism, and bifid uvula or cleft palate and is caused by heterozygous mutations in the genes encoding transforming growth factor beta receptors 1 and 2 (TGFBR1 and TGFBR2, respectively).
Although arterial tortuosity has been primarily described in Loeys-Dietz syndrome due to TGFBR1 and TGFBR2 mutations and in arterial tortuosity syndrome due to SLC210A mutations, recent studies that use quantitative measures of tortuosity suggest that tortuosity is present in many other genetic conditions associated with aortic dilation and dissection.
Although arterial tortuosity has been primarily described in Loeys-Dietz syndrome due to TGFBR1 and TGFBR2 mutations and in arterial tortuosity syndrome due to SLC210A mutations, recent studies that use quantitative measures of tortuosity suggest that tortuosity is present in many other genetic conditions associated with aortic dilation and dissection.
The disease is characterized by the triad of arterial tortuosity and aneurysms, hypertelorism, and bifid uvula or cleft palate and is caused by heterozygous mutations in the genes encoding transforming growth factor beta receptors 1 and 2 (TGFBR1 and TGFBR2, respectively).
We identified the novel heterozygous c.1165dupA mutation in exon 7 of TGFB2 in three members of a family, a 51-year-old male, his brother and nephew with aortic aneurysms, cervical arterial tortuosity and/or skeletal abnormalities as well as craniofacial dysmorphisms.
AOS, caused by pathogenic SMAD3 variants, is a recently described autosomal dominant syndrome characterized by aneurysms and arterial tortuosity in combination with osteoarthritis.
It became evident in recent years that mutations in the COL4A3 or the COL4A4 gene can give rise not only to autosomal recessive ATS syndrome, in which males and females are severely affected, but also to an autosomal dominant form, where the clinical progression towards impaired renal function can be very slow and also to benign familial hematuria (BFH) in which renal function is preserved.
Transport of dehydroascorbic acid is impaired in the endomembranes of fibroblasts from arterial tortuosity syndrome (ATS) patients, due to the mutation in the gene coding for glucose transporter GLUT10.
Expression of exogenous, tagged GLUT10 in fibroblasts from an ATS patient revealed a strict co-localization with the ER marker protein disulfide isomerase (PDI).
Glucose transporter 10 (GLUT10) is a member of the GLUT family of membrane transporters, and mutations in this gene cause arterial tortuosity syndrome (ATS).