Dataset Information

Molecular Genetics and Modifier Genes in Pseudoxanthoma Elasticum, a Heritable Multisystem Ectopic Mineralization Disorder.

ABSTRACT: In the past two decades, there has been great progress in identifying the molecular basis and pathomechanistic details in pseudoxanthoma elasticum (PXE), a heritable multisystem ectopic mineralization disorder. Although the identification of pathogenic variants in ABCC6 has been critical for understanding the disease process, genetic modifiers have been disclosed that explain the phenotypic heterogeneity of PXE. Adding to the genetic complexity of PXE are PXE-like phenotypes caused by pathogenic variants in other ectopic mineralization-associated genes. This review summarizes the current knowledge of the genetics and candidate modifier genes in PXE, a multifactorial disease at the genome-environment interface.

SUBMITTER: Luo H

PROVIDER: S-EPMC8068569 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Molecular Genetics and Modifier Genes in Pseudoxanthoma Elasticum, a Heritable Multisystem Ectopic Mineralization Disorder.

Luo Hongbin H Faghankhani Masoomeh M Cao Yi Y Uitto Jouni J Li Qiaoli Q

The Journal of investigative dermatology 20201217 5

In the past two decades, there has been great progress in identifying the molecular basis and pathomechanistic details in pseudoxanthoma elasticum (PXE), a heritable multisystem ectopic mineralization disorder. Although the identification of pathogenic variants in ABCC6 has been critical for understanding the disease process, genetic modifiers have been disclosed that explain the phenotypic heterogeneity of PXE. Adding to the genetic complexity of PXE are PXE-like phenotypes caused by pathogenic ...[more]

PMID: 33341249

Similar Datasets

Project description:ObjectivePseudoxanthoma elasticum (PXE) is a multisystem heritable disorder caused by mutations in the Abcc6 gene. The disease is characterized by ectopic mineralization of the skin, eyes, and arterial blood vessels. Previous studies have suggested that cardiovascular complications in patients with PXE are caused in part by premature atherosclerosis. The aim of this study is to determine the effect of an atherogenic diet on ectopic mineralization.MethodsWe used Abcc6 tm1JfK mice (Abcc6 -/- mice) as an established preclinical model of PXE. The offspring at age of 4 weeks were divided into two groups and fed the standard control laboratory diet (control group) and the atherogenic diet. Serum lipid profiles and bile acids were measured, and steatosis and tissue mineralization were evaluated by histopathologic analysis and chemical calcium quantification assay, respectively.ResultsAfter 50-58 weeks of feeding an atherogenic diet, the concentrations of total cholesterol, low-density lipoprotein/very-low-density lipoprotein cholesterol, and bile acids were significantly higher in the Abcc6 -/- mice on the atherogenic diet (180.9 ± 14.8 g/L, 145.9 ± 12.9 g/L, and 9.7 ± 1.4 μmol/L, respectively) than in Abcc6 -/- mice on a control diet (85.2 ± 4.8 g/L, 25.1 ± 5.5 g/L, and 3.3 ± 0.5 μmol/L, respectively) (P < 0.001). Hypercholesterolemia was accompanied by extensive lipid accumulation in the liver and aorta, a characteristic feature of steatosis. The direct calcium assay demonstrated significantly increased mineralization of the muzzle skin containing the dermal sheath of vibrissae (57.2 ± 4.4 μmol Ca/gram tissue on the atherogenic diet and 43.9 ± 2.2 μmol Ca/gram tissue on control diet; P < 0.01), a reproducible biomarker of the ectopic mineralization process in these mice. An increased frequency of mineralization was also observed in the kidneys and eyes of mice on the atherogenic diet (P < 0.01).ConclusionThese observations suggest that the atherogenic diet caused hypercholesterolemia and accelerated ectopic mineralization in the Abcc6 -/- mice. Our findings have clinical implications for patients with PXE, a currently intractable disorder with considerable morbidity and occasional mortality.

Dataset Information

Molecular Genetics and Modifier Genes in Pseudoxanthoma Elasticum, a Heritable Multisystem Ectopic Mineralization Disorder.

Publications

Molecular Genetics and Modifier Genes in Pseudoxanthoma Elasticum, a Heritable Multisystem Ectopic Mineralization Disorder.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets