A family exhibiting arterial tortuosity syndrome displays homozygosity for markers in the arterial tortuosity locus at chromosome 20q13

Abstract

Arterial tortuosity associated with hyperextensible skin and hypermobility of joints, features that are characteristics of Ehlers-Danlos syndrome (EDS), has been described in several families. An arterial tortuosity locus has recently been mapped to chromosome 20q13. Here, we report a consanguineous Kurdish family in which an affected child manifested elongation and severe tortuosity of the aorta, carotid, and other arteries. Additional clinical symptoms include loose skin, hypermobile joints, hernias, and facial features that resemble EDS individuals. To examine whether the arterial tortuosity locus was involved in this child, homozygosity analysis was performed using microsatellite markers on 20q13. The affected child was found homozygous, whereas the unaffected parents and three siblings were heterozygous. Additional typing defined the genomic interval to a 37-cm region within which the arterial tortuosity locus is located. Three functional candidate genes (B4GALT5, KCNB1, and PTGIS) were sequenced. No mutations were discovered in the coding regions of these three genes and the promoter regions of B4GALT5 and KCNB1 genes. Moreover, the B4GALT5 mRNA expression was unaltered in patient-derived lymphoblastoid cells. In the PTGIS gene promoter, the affected child was homozygous for eight variable number of tandem repeats, while parents and unaffected siblings carried six repeats.

Cutis laxa: A review

“…66,67 Arterial tortuosity syndrome ATS (MIM208050) is an autosomal recessive condition characterized by elongation and tortuosity of major arteries and variable skin laxity. [68][69][70][71][72][73][74] Distinctive complications include vascular aneurysms, dissections, and stenoses. [70][71][72]74 Death may occur in early childhood, 71 although milder phenotypes have been described.…”

“…[68][69][70][71][72][73][74] Distinctive complications include vascular aneurysms, dissections, and stenoses. [70][71][72]74 Death may occur in early childhood, 71 although milder phenotypes have been described. 74 ATS is caused by inactivating mutations in SLC2A10, which encodes GLUT10, a member of the glucose transporter family.…”

Arterial tortuosity syndrome: clinical and molecular findings in 12 newly identified families

“…Patients usually present with characteristic dysmorphic features including an elongated face, blepharophimosis and downslanting palpebral fissures, a beaked nose, a highly arched palate, and micrognathia. Other connective tissue manifestations comprise a soft, hyperextensible skin and skeletal abnormalities such as arachnodactyly, pectus deformity, joint laxity, and contractures [Abdul Wahab et al, 2003;Beuren et al, 1969;Ertugrul, 1967;Franceschini et al, 2000;Gardella et al, 2004;Lees et al, 1969;Meyer et al, 2005;Pletcher et al, 1996;Rivera et al, 2000;Welch et al, 1971;Wessels et al, 2004;Zaidi et al, 2005]. Patients are prone to aneurysm formation, dissections, and ischemic events [Abdul Wahab et al, 2003;Ades et al, 1996;Al Fadley et al, 2000;Lees et al, 1969;Pletcher et al, 1996;Welch et al, 1971;Wessels et al, 2004].…”

Characterization of a distinct lethal arteriopathy syndrome in twenty-two infants associated with an identical, novel mutation in FBLN4 gene, confirms fibulin-4 as a critical determinant of human vascular elastogenesis

“…ARCL Type I is characterized by cutis laxa, pulmonary emphysema, umbilical and inguinal hernias and gastrointestinal and vesico-urinary tract diverticuli, described in association with mutations of fibulin-5 [8] [GenBank:BC022280.1] and fibulin-4 [9] [GenBank:AF109121.1]. Though each of these disorders has characteristic phenotypic features [2,3,5,7-16], the dominating common features are dilatation, elongation and tortuosity of the large and medium sized arteries.…”