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

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.

Automated summary

In the past two decades, significant progress has been made in understanding the molecular basis and pathomechanistic details of pseudoxanthoma elasticum (PXE). Genetic modifiers have been identified to explain the phenotypic heterogeneity of PXE, in addition to pathogenic variants in the ABCC6 gene. The genetic complexity of PXE is further complicated by PXE-like phenotypes caused by variants in other ectopic mineralization-associated genes.