The prevalence of pseudoxanthoma elasticum: Revised estimations based on genotyping in a high vascular risk cohort
Kranenburg, Guido; Baas, Annette F.; de Jong, Pim A.; Asselbergs, Folkert W.; Visseren, Frank L.J.; Spiering, Wilko; SMART Study Group
(2019) European Journal of Medical Genetics, volume 62, issue 2, pp. 90 - 92
(Article)
Abstract
Background: Pseudoxanthoma elasticum (PXE), an autosomal recessive systemic calcification disorder, is caused by mutations in the ABCC6-gene and associated with severe visual impairment and peripheral arterial disease. Given the progress in development of a therapy for PXE, more precise estimations of its prevalence are warranted. Methods: We genotyped the four
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most common ABCC6 mutations (c.3421C > T, c.4182delG, c.3775delT, c.2787+1G > T), together accounting for half of all ABCC6 mutations identified in PXE patients from the Dutch population, in a Dutch high vascular risk cohort (n = 7893). The obtained allele frequencies were used to estimate the prevalence of PXE using the Hardy-Weinberg equilibrium. Results: The carrier frequency of ABCC6 was 0.60% for c.3421C > T, 0.17% for c.4182delG, 0.05% for c.3775delT and 0.03% for c.2787+1G > T. The prevalence of PXE based upon the allele frequencies of these four mutations was estimated as 1 per 56,000 (95%CI 1 per 35,000–97,000). Conclusion: The prevalence of PXE is at least 1 per 56,000 meaning that there would be at least 307 affected individuals in the Netherlands that may benefit from a potential upcoming treatment. Since this estimate is based on mutations together accounting for half of all ABCC6 mutations identified among PXE patients, the actual prevalence will probably be higher.
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Keywords: ABCC6, Prevalence, Pseudoxanthoma elasticum, Multidrug Resistance-Associated Proteins/genetics, Netherlands, Gene Frequency, Humans, Heterozygote, Pseudoxanthoma Elasticum/epidemiology, Genetic Carrier Screening, Polymorphism, Genetic, Genetics(clinical), Genetics, Journal Article
ISSN: 1769-7212
Publisher: Elsevier Masson SAS
Note: Funding Information: We gratefully acknowledge D. Dooijes (clinical laboratory geneticist) for his help with available genetic databases. Also, we gratefully acknowledge the SMART research nurses; R. van Petersen (data-manager); B.G.F. Dinther (vascular manager) and the participants of the SMART Study Group: A. Algra MD,PhD; Y. van der Graaf, MD,PhD; D.E. Grobbee, MD,PhD; G.E.H.M. Rutten, MD,PhD, Julius Center for Health Sciences and Primary care; F.L.J.Visseren, MD,PhD, Department of Internal Medicine; G.J. de Borst, MD,PhD, Department of Vascular Surgery; L.J. Kappelle, MD,PhD, Department of Neurology; T. Leiner, MD,PhD, Department of Radiology; P.A. Doevendans, MD,PhD, Department of Cardiology. Publisher Copyright: © 2018
(Peer reviewed)