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

• Published in: Clinical genetics Vol. 67; no. 2; pp. 183 - 188
• Main Authors: Zaidi, SHE, Peltekova, V, Meyer, S, Lindinger, A, Paterson, AD, Tsui, L-C, Faiyaz-Ul-Haque, M, Teebi, AS
• Format: Journal Article
• Language: English
• Published: Oxford, UK; Malden, USA Munksgaard International Publishers 01-02-2005; Blackwell; Blackwell Publishing Ltd
• Subjects: Angiography; arterial tortuosity; Arteries - abnormalities; Biological and medical sciences; Chromosomes, Human, Pair 20; connective tissue disorder; DNA Mutational Analysis; Ehlers-Danlos syndrome; Ehlers-Danlos Syndrome - genetics; Ethnicity; Families & family life; Gene Expression Profiling; General aspects. Genetic counseling; Genetics; Haplotypes; homozygosity mapping; Humans; Infant; Male; Medical disorders; Medical genetics; Medical sciences; Microsatellite Repeats; Pedigree; Promoter Regions, Genetic; Reverse Transcriptase Polymerase Chain Reaction; Tandem Repeat Sequences; Human; Ehlers-Danlos syndrome; arterial tortuosity; Family study; Tortuosity; Biological marker; Chromosome; Homozygosity; connective tissue disorder; homozygosity mapping; Artery; Syndrome; Family environment; Genetics; Locus
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1111/j.1399-0004.2004.00391.x

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.