EMILIN1 deficiency causes arterial tortuosity with osteopenia and connects impaired elastogenesis with defective collagen fibrillogenesis.
Christin S Adamo, Aude Beyens, Alvise Schiavinato, Douglas R Keene, Sara F Tufa, Matthias Mörgelin, Jürgen Brinckmann, Takako Sasaki, Anja Niehoff, Maren Dreiner, Lore Pottie, Laura Muiño-Mosquera, Elif Yilmaz Gulec, Alper Gezdirici, Paola Braghetta, Paolo Bonaldo, Raimund Wagener, Mats Paulsson, Helen Bornaun, Riet De Rycke, Michiel De Bruyne, Femke Baeke, Walter P Devine, Balram Gangaram, Allison Tam, Meena Balasubramanian, Sian Ellard, Sandra Moore, Sofie Symoens, Joseph Shen, Stacey Cole, Ulrike Schwarze, Kathryn W Holmes, Susan J Hayflick, Wojciech Wiszniewski, Sheela Nampoothiri, Elaine C Davis, Lynn Y Sakai, Gerhard Sengle, Bert Callewaert
American journal of human genetics 2022 Dec 01EMILIN1 (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. Copyright © 2022 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
Citation
Christin S Adamo, Aude Beyens, Alvise Schiavinato, Douglas R Keene, Sara F Tufa, Matthias Mörgelin, Jürgen Brinckmann, Takako Sasaki, Anja Niehoff, Maren Dreiner, Lore Pottie, Laura Muiño-Mosquera, Elif Yilmaz Gulec, Alper Gezdirici, Paola Braghetta, Paolo Bonaldo, Raimund Wagener, Mats Paulsson, Helen Bornaun, Riet De Rycke, Michiel De Bruyne, Femke Baeke, Walter P Devine, Balram Gangaram, Allison Tam, Meena Balasubramanian, Sian Ellard, Sandra Moore, Sofie Symoens, Joseph Shen, Stacey Cole, Ulrike Schwarze, Kathryn W Holmes, Susan J Hayflick, Wojciech Wiszniewski, Sheela Nampoothiri, Elaine C Davis, Lynn Y Sakai, Gerhard Sengle, Bert Callewaert. EMILIN1 deficiency causes arterial tortuosity with osteopenia and connects impaired elastogenesis with defective collagen fibrillogenesis. American journal of human genetics. 2022 Dec 01;109(12):2230-2252
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PMID: 36351433
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