Guido Kranenburg1, Annette F Baas2, Pim A de Jong3, Folkert W Asselbergs4, Frank L J Visseren1, Wilko Spiering5. 1. Department of Vascular Medicine, University Medical Center Utrecht, Utrecht University, the Netherlands. 2. Department of Medical Genetics, University Medical Center Utrecht, Utrecht University, the Netherlands. 3. Department of Radiology, University Medical Center Utrecht, Utrecht University, the Netherlands. 4. Department of Cardiology, University Medical Center Utrecht, Utrecht University, the Netherlands. 5. Department of Vascular Medicine, University Medical Center Utrecht, Utrecht University, the Netherlands. Electronic address: W.Spiering@umcutrecht.nl.
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 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.
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 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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