title: Arterial tortuosity syndrome: clinical and molecular findings in 12 newly identified families.
abstract: Arterial tortuosity syndrome (ATS) is a rare autosomal recessive connective tissue disease, characterized by widespread arterial involvement with elongation, tortuosity, and aneurysms of the large and middle-sized arteries. Recently, SLC2A10 mutations were identified in this condition. This gene encodes the glucose transporter GLUT10 and was previously suggested as a candidate gene for diabetes mellitus type 2. A total of 12 newly identified ATS families with 16 affected individuals were clinically and molecularly characterized. In addition, extensive cardiovascular imaging and glucose tolerance tests were performed in both patients and heterozygous carriers. All 16 patients harbor biallelic SLC2A10 mutations of which nine are novel (six missense, three truncating mutations, including a large deletion). Haplotype analysis suggests founder effects for all five recurrent mutations. Remarkably, patients were significantly older than those previously reported in the literature (P=0.04). Only one affected relative died, most likely of an unrelated cause. Although the natural history of ATS in this series was less severe than previously reported, it does indicate a risk for ischemic events. Two patients initially presented with stroke, respectively at age 8 months and 23 years. Tortuosity of the aorta or large arteries was invariably present. Two adult probands (aged 23 and 35 years) had aortic root dilation, seven patients had localized arterial stenoses, and five had long stenotic stretches of the aorta. Heterozygous carriers did not show any vascular anomalies. Glucose metabolism was normal in six patients and eight heterozygous individuals of five families. As such, overt diabetes is not related to SLC2A10 mutations associated with ATS.
authors.affiliation: Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors.forename: B L
authors.initials: BL
authors.lastname: Callewaert
authors.forename: A
authors.initials: A
authors.lastname: Willaert
authors.forename: W S
authors.initials: WS
authors.lastname: Kerstjens-Frederikse
authors.forename: J
authors.initials: J
authors.lastname: De Backer
authors.forename: K
authors.initials: K
authors.lastname: Devriendt
authors.forename: B
authors.initials: B
authors.lastname: Albrecht
authors.forename: M A
authors.initials: MA
authors.lastname: Ramos-Arroyo
authors.forename: M
authors.initials: M
authors.lastname: Doco-Fenzy
authors.forename: R C M
authors.initials: RC
authors.lastname: Hennekam
authors.forename: R E
authors.initials: RE
authors.lastname: Pyeritz
authors.forename: O N
authors.initials: ON
authors.lastname: Krogmann
authors.forename: G
authors.initials: G
authors.lastname: Gillessen-kaesbach
authors.forename: E L
authors.initials: EL
authors.lastname: Wakeling
authors.forename: S
authors.initials: S
authors.lastname: Nik-zainal
authors.forename: C
authors.initials: C
authors.lastname: Francannet
authors.forename: P
authors.initials: P
authors.lastname: Mauran
authors.forename: C
authors.initials: C
authors.lastname: Booth
authors.forename: M
authors.initials: M
authors.lastname: Barrow
authors.forename: R
authors.initials: R
authors.lastname: Dekens
authors.forename: B L
authors.initials: BL
authors.lastname: Loeys
authors.forename: P J
authors.initials: PJ
authors.lastname: Coucke
authors.forename: A M
authors.initials: AM
authors.lastname: De Paepe
mesh_terms: D000328:Adult; D001158:Arteries / Q000002:abnormalities*; D003240:Connective Tissue Diseases / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism; D005190:Family; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D018810:Magnetic Resonance Angiography; D008954:Models, Biological; D010375:Pedigree; D010641:Phenotype; D013577:Syndrome
chemical_list: D051246:Glucose Transport Proteins, Facilitative; C430746:SLC2A10 protein, human; D005947:Glucose