Mutations in Fibronectin Cause a Subtype of Spondylometaphyseal Dysplasia with "Corner Fractures"

American Journal of Human Genetics
Chae Syng LeePhilippe M Campeau

Abstract

Fibronectin is a master organizer of extracellular matrices (ECMs) and promotes the assembly of collagens, fibrillin-1, and other proteins. It is also known to play roles in skeletal tissues through its secretion by osteoblasts, chondrocytes, and mesenchymal cells. Spondylometaphyseal dysplasias (SMDs) comprise a diverse group of skeletal dysplasias and often manifest as short stature, growth-plate irregularities, and vertebral anomalies, such as scoliosis. By comparing the exomes of individuals with SMD with the radiographic appearance of "corner fractures" at metaphyses, we identified three individuals with fibronectin (FN1) variants affecting highly conserved residues. Furthermore, using matching tools and the SkelDys emailing list, we identified other individuals with de novo FN1 variants and a similar phenotype. The severe scoliosis in most individuals and rare developmental coxa vara distinguish individuals with FN1 mutations from those with classical Sutcliffe-type SMD. To study functional consequences of these FN1 mutations on the protein level, we introduced three disease-associated missense variants (p.Cys87Phe [c.260G>T], p.Tyr240Asp [c.718T>G], and p.Cys260Gly [c.778T>G]) into a recombinant secreted N-terminal 70 kD...Continue Reading

References

Jun 14, 1990·Nature·M BaronI D Campbell
Aug 1, 1997·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·D R KeeneL Y Sakai
Jun 24, 1998·American Journal of Medical Genetics·T DuettingJ Spranger
Jan 29, 1999·Matrix Biology : Journal of the International Society for Matrix Biology·J T HechtP J Duke
Sep 24, 2002·Journal of Cell Science·Roumen Pankov, Kenneth M Yamada
Oct 26, 2002·The Journal of Biological Chemistry·Guoqing LinDieter P Reinhardt
May 9, 2003·Nature·Ulrich Schwarz-LinekJennifer R Potts
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Jan 25, 2005·American Journal of Medical Genetics. Part a·V Reid SuttonPaula W Brill
May 20, 2006·Arteriosclerosis, Thrombosis, and Vascular Biology·Deane F Mosher
Dec 14, 2006·American Journal of Medical Genetics. Part a·Kerstin WalterSheila Unger
Apr 28, 2007·The EMBO Journal·Ioannis VakonakisIain D Campbell
May 23, 2007·The Journal of Biological Chemistry·Karen K McKeePeter D Yurchenco
Feb 13, 2008·Proceedings of the National Academy of Sciences of the United States of America·Federica CastellettiMarina Noris
Aug 21, 2008·Proceedings of the National Academy of Sciences of the United States of America·Richard J BinghamJennifer R Potts
Nov 28, 2008·Molecular Biology of the Cell·Laetitia SabatierDieter P Reinhardt
Aug 10, 2010·Annual Review of Cell and Developmental Biology·Purva SinghJean E Schwarzbauer
Sep 15, 2012·Journal of Cell Science·Purva Singh, Jean E Schwarzbauer
Dec 12, 2012·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·Dilek Ertoy BaydarRossella Piras
Apr 9, 2016·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Hiromi OhtsuboShun-Ichi Nakamura
Nov 27, 2016·American Journal of Medical Genetics. Part a·Keren MacholLindsay C Burrage

❮ Previous
Next ❯

Citations

May 23, 2018·Current Opinion in Pediatrics·Youn Hee JeeOla Nilsson
May 26, 2018·Current Opinion in Clinical Nutrition and Metabolic Care·Nika LovšinJanja Marc
Apr 15, 2020·Child's Nervous System : ChNS : Official Journal of the International Society for Pediatric Neurosurgery·Dawid SzpechtAgnieszka Seremak-Mrozikiewicz
Nov 30, 2018·Journal of Cellular Biochemistry·Mengru ZengLi Xiao
Feb 17, 2019·Journal of Psychiatric Research·Karin Vanessa Carias, Rachel Wevrick
Nov 14, 2020·Radiographics : a Review Publication of the Radiological Society of North America, Inc·Atsuhiko HandaGen Nishimura

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.