Arterial tortuosity syndrome in two Italian paediatric patients

Marco Ritelli,Giovanni Puppini,Paolo Biban,Sergio Barlati,Maria Antonia Prioli,Mara Pilati,Marina Colombi,Mariano Vicchio,Bruno Drera

doi:10.1186/1750-1172-4-20

Abstract

BackgroundArterial tortuosity syndrome (ATS) (OMIM #208050) is a rare autosomal recessive connective tissue disorder characterized by tortuosity and elongation of the large and medium-sized arteries, propensity to aneurysms formation, vascular dissection, and pulmonary arteries stenosis. ATS is caused by mutations in SLC2A10 gene, encoding for the facilitative glucose transporter 10 (GLUT10). So far, 17 SLC2A10 mutations have been reported in 32 families, two of which were Italian with a total of five patients. Here we present the clinical and molecular characterization of two novel Italian paediatric ATS patients.MethodsThe exons and intronic flanking regions of SLC2A10 gene were amplified and direct sequencing was performed.ResultsIn both patients, the involvement of major- and medium-sized arteries was characteristic; the nonvascular connective tissue manifestations were mild and not pathognomic of the disorder. Both patients, born from non-consanguineous parents, were heterozygous for two different SLC2A10 mutations, three of which were recurrent and one was novel (p.Arg231Trp). This mutation is localized at the endofacial loop between the transmembrane domains 6 and 7 of GLUT10.ConclusionTwo novel ATS patients were characterized at clinical and molecular level. Overall, four ATS unrelated families are known in Italy so far. Though ATS clinical delineation improved in the last years, further works in the comprehension of disease presentation and complications onset, particularly in paediatric age, and on ATS molecular basis are needed to add new insights for diagnosis and prevention strategies for related complications.

Highlights

Arterial tortuosity syndrome (ATS) (OMIM #208050) is a rare autosomal recessive connective tissue disorder characterized by tortuosity and elongation of the large and mediumsized arteries, propensity to aneurysms formation, vascular dissection, and pulmonary arteries stenosis
Arterial tortuosity syndrome (ATS) (OMIM #208050) is an extremely rare autosomal recessive disorder characterized by tortuosity and elongation of the large and medium-sized arteries, propensity to aneurysms formation, vascular dissection, and pulmonary arteries stenosis
ATS is due to mutations in SLC2A10 gene, located on chromosome 20q13.1 and encoding for the 541 amino acid facilitative glucose transporter 10 (GLUT10), consisting in 12 transmembrane hydrophobic segments connected by 5 intracellular and 6 extracellular loops [5,6]

Summary

Results

The involvement of major- and medium-sized arteries was characteristic; the nonvascular connective tissue manifestations were mild and not pathognomic of the disorder. Both patients, born from non-consanguineous parents, were heterozygous for two different SLC2A10 mutations, three of which were recurrent and one was novel (p.Arg231Trp). Born from non-consanguineous parents, were heterozygous for two different SLC2A10 mutations, three of which were recurrent and one was novel (p.Arg231Trp) This mutation is localized at the endofacial loop between the transmembrane domains 6 and 7 of GLUT10

Conclusion

Background