Faiyaz-Ul-Haque M, etal., Atherosclerosis. 2009 Apr;203(2):466-71. doi: 10.1016/j.atherosclerosis.2008.07.026. Epub 2008 Aug 5.
Arterial tortuosity syndrome is an autosomal recessive disorder characterized by severe tortuosity of greater and systemic arteries in affected individuals. In addition, patients display connective tissue features which include hyperextensible skin, hypermobility of joints and characteristic facial
features. This syndrome is caused by mutation in SLC2A10 gene which encodes for the facilitative glucose transporter, GLUT10. We describe seven patients of two unrelated Saudi Arabian families who display tortuosity, dilatation and stenosis of arteries, pulmonary hypertension and other cardiovascular manifestations. These patients exhibit characteristic connective tissue phenotypes and distinctive facial features. In the single patient of Family 1, sequencing of the candidate gene, SLC2A10, identified a novel missense c.313C>T mutation encoding a p.Arg105Cys substitution in the second extracellular domain of GLUT10. The Arg105 in GLUT10 is highly conserved across species and its replacement with cysteine is predicted to be pathogenic. In the second family, all of the six affected individuals carry recurrent c.243C>G missense mutation encoding a p.Ser81Arg change in the third transmembrane domain of GLUT10. The present study suggests that there exists an intra- and inter-familial phenotypic variability in arterial tortuosity patients carrying identical or different mutations in SLC2A10 gene. While skin hyperextensibility, small joint hypermobility, and facial features are similarly expressed in these patients, there is a range of other phenotypes which include arterial tortuosity and associated complications, and abnormalities of other organs.
Arterial tortuosity syndrome (ATS) is a rare autosomal recessive disorder in which patients display tortuosity of arteries in addition to hyperextensible skin, joint laxity, and other connective tissue features. This syndrome is caused by mutations in the SLC2A10
> gene. In this article we describe an ATS girl of Kurdish origin who, in addition to arterial tortuosity and connective tissue features, displays stomach displacement within the thorax and bilateral hip dislocation. Clinical details of this patient have been reported previously. Sequencing of the SLC2A10 gene identified a novel homozygous non-sense c.756C>A mutation in this patient's DNA. This mutation in the SLC2A10 gene replaces a cysteine encoding codon with a stop signal. This is believed to cause a premature truncation of GLUT10 protein in this patient. We conclude that patients of Kurdish origin who display arterial tortuosity associated with skin hyperextensibility, joint hypermobility, and characteristic facial features may carry mutations in the SLC2A10 gene.
Castori M, etal., Am J Med Genet A. 2012 May;158A(5):1164-9. doi: 10.1002/ajmg.a.35266. Epub 2012 Apr 9.
Arterial tortuosity syndrome (ATS) is an autosomal recessive connective tissue disorder, mainly characterized by tortuosity and elongation of the large- and medium-sized arteries with predisposition to stenoses and aneurysms. ATS is caused by mutations in the SLC2A10
span> gene, encoding for the facilitative glucose transporter 10 (GLUT10) and is described typically in pediatric patients. We report on a 51-year-old woman, originally ascertained because of unexplained widespread chronic pain and positive family history of aortic malformation. The main findings included aged appearance, congenital joint hypermobility, joint instability complications, chronic fatigue syndrome, progressive painful joint stiffness, abdominal hernias, pelvic prolapses, multiple cardiac valve prolapses, varicose veins, easy bruising, and gingival recession. Vascular imaging revealed kinking and anomalous origin of the aortic arch branches, marked tortuosity of the aorta, pulmonary and most middle arteries, and a small aneurysm of the splenic artery. SLC2A10 analysis disclosed homozygosity for the novel c.1411+1G>A splice mutation, leading to a 41 amino acids GLUT10 internal deletion. Expression study by immunofluorescence using healthy control cells showed lack of membrane internalization of GLUT10 in patient's skin fibroblasts. This report describes the first splice-site SLC2A10 mutation and increases to 19 the repertoire of known mutations in this gene. Comparison with the few previously published adult patients with ATS contributes to the natural history of this condition, which is probably under diagnosed within the expanding family of inherited connective tissue disorders.
Takahashi Y, etal., Am J Med Genet A. 2013 Apr;161A(4):856-9. doi: 10.1002/ajmg.a.35776. Epub 2013 Mar 12.
We report on a 2-year-old Japanese boy with early-onset pulmonary emphysema, exhibiting dysmorphic face, loose skin, and inguinal and Morgagni hernias. He was admitted to our hospital owing to refractory respiratory infection. On the basis of his clinical features, we investigated the SLC2A10
font-weight:700;'>SLC2A10 gene and identified novel compound heterozygous mutations of c.417T > A and c.692G > A, leading to the diagnosis of artery tortuosity syndrome (ATS). This syndrome is an extremely rare autosomal recessive disorder characterized by tortuosity and elongation of the large and medium-sized arteries, hyperextensible skin, and diverse hernias, mostly reported from Europe and Middle Eastern countries, but not from Asia. Although chronic obstructive pulmonary disease, namely, emphysema, has not been well documented in ATS, it may be likely because TGF-beta up-regulation is known to be evoked by SLC2A10 mutations, resulting in reconstruction of pulmonary endothelial cells and emphysema. This is the first report of ATS associated with early-onset pulmonary emphysema, suggesting that patients with ATS may also require close attention for chronic obstructive pulmonary disease.
