ABCMdb

PMID: 12649085

Germain DP, Boutouyrie P, Laloux B, Laurent S
Arterial remodeling and stiffness in patients with pseudoxanthoma elasticum.
Arterioscler Thromb Vasc Biol. 2003 May 1;23(5):836-41. Epub 2003 Mar 20., 2003-05-01 [PubMed]

Sentences

No. Mutations Sentence Comment

13 ABCC6 p.Arg1141* Vascular involvement is common, and patients with PXE typically present with arteriosclerosis, hypertension, transient ischemic attacks, and occlusive vascular changes at young ages.2 Cardiovascular complications, mainly coronary artery disease, are rare but can be life threatening.2 The estimated prevalence of PXE is 1 in 70 000 to 100 000.3 Although autosomal recessive inheritance (OMIM 264800) is most frequently found in PXE, autosomal dominant segregation (OMIM 177850) has also been proposed.4 The PXE locus has been mapped to chromosome 16p13.1, and mutations in the ABCC6 gene (previously known as MRP6 or eMOAT), encoding a 1503-amino acid putative membrane transporter of unknown function, have recently been simultaneously disclosed by 5 research groups as the genetic defect responsible for PXE.5-9 The existence of pseudogenes has been subsequently documented.10-13 The R1141X mutation in the ABCC6 gene is associated with a sharply increased risk of premature coronary artery disease.14 Histopathology of biopsies from clinically affected skin shows morphologically altered elastic fibers, which are fragmented and swollen and appear calcified when examined by special stains (eg, von Kossa), whereas PXE has also been characterized by proteoglycans accumulation, including heparan-sulfate and chondroitin-6-sulfate proteoglycans, glycosaminoglycan hyaluronic acid, decorin, and biglycan.15-17 Despite identification of the genetic defect, little is known about the pathogenesis of vascular lesions in PXE and the means for preventing arterial complications in young adults. Login to comment 29 ABCC6 p.Arg1141* Various mutations were identified, among which the nonsense R1141X was the most prevalent. Login to comment