Submission Details

SLC2A10 has been reported in association with autosomal recessive arterial tortuosity syndrome (ATS) in at least 106 individuals (Callewaert B, De Paepe A, Coucke P, GeneReviews, 2023). Clinical phenotypes of ATS include aortic tortuosity, tortuosity of large and mid-sized arteries, pulmonary artery stenosis, joint hypermobility, ocular abnormalities, and characteristic facial features. Phenotype severity ranges from neonatal lethality to adults with isolated phenotypes. Aortic aneurysms varied from very slowly progressive to rapid dilation and dissection. 14 variants (missense, nonsense, deletion, and frameshift) reported in 10 probands in 4 publications (PMIDs: 17935213, 18818946, 37619836, 29323665) are included in this curation. The mechanism of pathogenicity is loss of function. This gene-disease association is also supported by experimental evidence including protein expression in the aorta (PMID:23715323) and a mouse model double knock out for both SLC2A10 and Gulo that recapitulated isolated phenotypes of ATS including decreases in diameter in the descending aorta and compromised extracellular matrix formation (PMID:32307537). Finally the curation is supported by the biochemical function of SLC2A10, which encodes GLUT10, a glucose transporting protein that transports dehydroascorbic acid (DHA). Phenotypes from variants in SLC2A10 may be a result of impaired vitamin C cellular compartmentalization, increases in ROS/oxidative stress, and defective TGF-B signaling. In summary, SLC2A10 is definitively associated with autosomal recessive arterial tortuosity syndrome. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. The evidence summary was approved by the Heritable Thoracic Aortic Aneurysm and Dissection subgroup of the Hereditary Cardiovascular Disease Gene Curation Expert Panel on 9/6/2024.