A novel missense and a recurrent mutation in SLC2A10 gene of patients affected with arterial tortuosity syndrome

• Published in: Atherosclerosis Vol. 203; no. 2; pp. 466 - 471
• Main Authors: Faiyaz-Ul-Haque, Muhammad, Zaidi, Syed H.E, Al-Sanna, Nouriyah, Alswaid, Abdulrahman, Momenah, Tariq, Kaya, Namik, Al-Dayel, Fouad, Bouhoaigah, Issam, Saliem, Mohammed, Tsui, Lap-Chee, Teebi, Ahmad S
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ireland Ltd 01.04.2009; Elsevier
• Subjects: Arterial tortuosity syndrome; Arteries - pathology; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cardiovascular; Cardiovascular system; Connective Tissue Diseases - genetics; Connective tissue disorder; Constriction, Pathologic; DNA Mutational Analysis; Family Health; Female; Glucose Transport Proteins, Facilitative - genetics; Homozygote; Humans; Male; Medical sciences; Mutation; Mutation, Missense; Pharmacology. Drug treatments; Phenotype; Pulmonary hypertension; Saudi Arabia; SLC2A10 mutation; Syndrome; Vasodilator agents. Cerebral vasodilators; Saudi Arabia; Arterial tortuosity syndrome; Connective tissue disorder; Pulmonary hypertension; SLC2A10 mutation; Vascular disease; Human; Connective tissue; Missense mutation; Respiratory disease; Tortuosity; Atherosclerosis; Cardiovascular disease
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2008.07.026

Abstract 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.