We report on the preferential recruitment of the αvβ3 integrin, due to the lack of FN-ECM and its canonical integrin receptor, in dermal fibroblasts from Ehlers-Danlos syndromes (EDS) and arterial tortuosity syndrome (ATS), which are rare multisystem connective tissue disorders.
Glucose transporter 10 (GLUT10) is a member of the GLUT family of membrane transporters, and mutations in this gene cause arterial tortuosity syndrome (ATS).
Expression of exogenous, tagged GLUT10 in fibroblasts from an ATS patient revealed a strict co-localization with the ER marker protein disulfide isomerase (PDI).
Lack of vitamin C for lysyl- and prolyl-hydroxylase activity may explain the defects in collagen and elastin formation found in ATS, and draws strong parallels between ATS and scurvy.
COL4A1-associated disorders encompass a wide range of hereditary vasculopathy, including porencephaly and HANAC (adult-onset hemorrhagic stroke with cerebral aneurysm and retinal arterial tortuosity, renal cysts, and thenar muscle cramp).
The paternal COL4A5 mutation seems to account for the complete phenotype of ATS in the father and the maternal mutation in MYH9 for the inner ear deafness in the mother.
Linkage analysis of the genes involved in EDS and other connective tissue disorders, excluded COL1A1, COL1A2, COL2A1, COL3A1, COL5A1, COL5A2, COL5A3, COL6A1, COL6A2, ADAMTS2, ELN, FN1, TNXA, and TNXB as candidate genes in the family under study, thus indicating that ATS is a distinct clinical and molecular entity.
We investigated the distribution of four genetic polymorphisms (angiotensin converting enzyme [ACE], methylenetetrahydrofolate reductase [MTHFR], apolipoprotein E [apo E], and paraoxonase [PON] genes) in 30 subjects with VaSA, 30 subjects with moderate carotid atherosclerosis (ATS group), and 161 controls with a negative history for cardiovascular disease.