Clinical utility gene card: for pseudoxanthoma elasticum

Legrand, Anne; Bénistan, Karelle; Mazzella, Jean‐Michaël; Adham, Salma; Frank, Michael; Jeunemaı̂tre, Xavier; Albuisson, Juliette

doi:10.1038/s41431-017-0090-2

Cited by 1 publication

(1 citation statement)

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“…In 8 clinically confirmed PXE patients only one or no ABCC6 variants was found. Since MLPA currently only covers 23 of the 31 coding exons of the ABCC6 gene, it might be that large deletions in the other eight exons were missed [38]. Since we excluded these patients from our genotype-phenotype analysis, this did not affect our results.…”

Section: Discussionmentioning

confidence: 99%

Genotype-phenotype correlation in pseudoxanthoma elasticum

et al. 2021

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Background and aims: Pseudoxanthoma elasticum (PXE) is caused by variants in the ABCC6 gene. It results in calcification in the skin, peripheral arteries and the eyes, but has considerable phenotypic variability. We investigated the association between the ABCC6 genotype and calcification and clinical phenotypes in these different organs. Methods: ABCC6 sequencing was performed in 289 PXE patients. Genotypes were grouped as two truncating, mixed, or two non-truncating variants. Arterial calcification mass was quantified on whole body, low dose CT scans; and peripheral arterial disease was measured with the ankle brachial index after treadmill test. The presence of pseudoxanthoma in the skin was systematically scored. Ophthalmological phenotypes were the length of angioid streaks as a measure of Bruchs membrane calcification, the presence of choroidal neovascularizations, severity of macular atrophy and visual acuity. Regression models were built to test the age and sex adjusted genotype-phenotype association. Results: 158 patients (median age 51 years) had two truncating variants, 96 (median age 54 years) a mixed genotype, 18 (median age 47 years) had two non-truncating variants. The mixed genotype was associated with lower peripheral (β: 0.39, 95%CI:-0.62;-0.17) and total (β: 0.28, 95%CI:-0.47;-0.10) arterial calcification mass scores, and lower prevalence of choroidal neovascularizations (OR: 0.41 95%CI:0.20; 0.83) compared to two truncating variants. No association with pseudoxanthomas was found. Conclusions: PXE patients with a mixed genotype have less severe arterial and ophthalmological phenotypes than patients with two truncating variants in the ABCC6 gene. Research into environmental and genetic modifiers might provide further insights into the unexplained phenotypic variability.

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Section: Discussionmentioning

confidence: 99%