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Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry
Published on: June 21, 2018
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Genotype-phenotype correlation in pseudoxanthoma elasticum.
Jonas W Bartstra1, Sara Risseeuw2, Pim A de Jong1
1Department of Radiology, University Medical Center Utrecht, Utrecht University, the Netherlands.
Atherosclerosis
|April 3, 2021
Summary
Pseudoxanthoma elasticum (PXE) patients with a mixed ABCC6 genotype show reduced arterial calcification and fewer eye complications compared to those with two truncating variants. This suggests genotype influences PXE severity.
Area of Science:
- Genetics and Molecular Biology
- Medical Research
- Ophthalmology
Background:
- Pseudoxanthoma elasticum (PXE) is a genetic disorder caused by variants in the ABCC6 gene.
- PXE leads to calcification in skin, arteries, and eyes, exhibiting significant variability in clinical presentation.
- The relationship between specific ABCC6 genotypes and the manifestation of PXE phenotypes remains incompletely understood.
Purpose of the Study:
- To investigate the association between ABCC6 gene variants and the severity of calcification and clinical phenotypes in PXE patients.
- To analyze genotype-phenotype correlations across different organs affected by PXE, including skin, arteries, and eyes.
Main Methods:
- ABCC6 gene sequencing was conducted on 289 PXE patients, categorizing genotypes into two truncating, mixed, or two non-truncating variants.
- Arterial calcification was quantified using low-dose CT scans, and peripheral arterial disease was assessed via ankle-brachial index.
- Ophthalmological assessments included angioid streak length, choroidal neovascularization presence, macular atrophy, and visual acuity.
Main Results:
- Patients with a mixed genotype (n=96) exhibited significantly lower peripheral and total arterial calcification mass scores compared to those with two truncating variants (n=158).
- The mixed genotype was associated with a reduced prevalence of choroidal neovascularizations (OR: 0.41) compared to the two truncating variant group.
- No significant association was found between ABCC6 genotype and the presence of pseudoxanthomas in the skin.
Conclusions:
- PXE patients with a mixed ABCC6 genotype demonstrate less severe arterial and ophthalmological phenotypes than those with two truncating variants.
- These findings highlight the influence of specific ABCC6 genotypes on PXE disease manifestation.
- Further research into genetic and environmental modifiers is warranted to explain the observed phenotypic variability in PXE.
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