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Novel clinico‐molecular insights in pseudoxanthoma elasticum provide an efficient molecular screening method and a comprehensive diagnostic flowchart
Author(s) -
Vanakker Olivier M.,
Leroy Bart P.,
Coucke Paul,
Bercovitch Lionel G.,
Uitto Jouni,
Viljoen Dennis,
Terry Sharon F.,
Van Acker Petra,
Matthys Dirk,
Loeys Bart,
De Paepe Anne
Publication year - 2008
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.9514
Subject(s) - pseudoxanthoma elasticum , subclinical infection , population , disease , pathology , biology , stroke (engine) , medicine , bioinformatics , mechanical engineering , environmental health , engineering
Pseudoxanthoma elasticum (PXE) is a heritable connective tissue disorder characterized by ocular, cutaneous and cardiovascular manifestations. It is caused by mutations in the ABCC6 gene (chr. 16p13.1), encoding a transmembrane transporter protein, the substrate and biological function of which are currently unknown. A comprehensive clinical and molecular study of 38 Belgian PXE probands and 21 relatives (4 affected and 17 carriers) was performed. An extensive clinical evaluation protocol was implemented with serial fundus, skin and cardiovascular evaluation. We report on 14 novel mutations in the ABCC6 gene. We observed extensive variability in severity of both cutaneous and ocular lesions. The type of skin lesion however usually remained identical throughout the evolution of the disorder, while ophthalmological progression was mainly due to functional decline. Peripheral artery disease (53%) and stroke (15%) were significantly more prevalent than in the general population (10–30% and 0.3–0.5% respectively). Interestingly, we also observed a relatively high incidence of subclinical peripheral artery disease (41%) in our carrier population. We highlight the significance of peripheral artery disease and stroke in PXE patients as well as the subclinical manifestations in carriers. Through follow‐up data we gained insight into the natural history of PXE. We propose a cost‐ and time‐efficient two‐step method of ABCC6 analysis which can be used in different populations. Additionally, we created a diagnostic flowchart and attempted to define the role of molecular analysis of ABCC6 in the work‐up of a PXE patient. © 2007 Wiley‐Liss, Inc.