EMILIN1 deficiency causes arterial tortuosity with osteopenia and connects impaired elastogenesis with defective collagen fibrillogenesis

Am J Hum Genet. 2022 Dec 1;109(12):2230-2252. doi: 10.1016/j.ajhg.2022.10.010. Epub 2022 Nov 8.


EMILIN1 (elastin-microfibril-interface-located-protein-1) is a structural component of the elastic fiber network and localizes to the interface between the fibrillin microfibril scaffold and the elastin core. How EMILIN1 contributes to connective tissue integrity is not fully understood. Here, we report bi-allelic EMILIN1 loss-of-function variants causative for an entity combining cutis laxa, arterial tortuosity, aneurysm formation, and bone fragility, resembling autosomal-recessive cutis laxa type 1B, due to EFEMP2 (FBLN4) deficiency. In both humans and mice, absence of EMILIN1 impairs EFEMP2 extracellular matrix deposition and LOX activity resulting in impaired elastogenesis, reduced collagen crosslinking, and aberrant growth factor signaling. Collagen fiber ultrastructure and histopathology in EMILIN1- or EFEMP2-deficient skin and aorta corroborate these findings and murine Emilin1-/- femora show abnormal trabecular bone formation and strength. Altogether, EMILIN1 connects elastic fiber network with collagen fibril formation, relevant for both bone and vascular tissue homeostasis.

Keywords: EFEMP2; EMILIN1; LOX; aortic aneurysm; arterial tortuosity; collagen; cutis laxa; elastic fiber; extracellular matrix; fracture.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Diseases, Metabolic*
  • Collagen / genetics
  • Cutis Laxa* / genetics
  • Elastin / metabolism
  • Extracellular Matrix Proteins / metabolism
  • Humans
  • Mice


  • Collagen
  • Elastin
  • elastin microfibril interface located protein
  • Extracellular Matrix Proteins

Supplementary concepts

  • Arterial Tortuosity Syndrome