The pathogenesis and intersecting mechanisms of monogenic bone mass disorders

Hendrickx, G., Boudin, E. & Van Hul, W. A look behind the scenes: the risk and pathogenesis of primary osteoporosis. Nat. Rev. Rheumatol. 11, 462–474 (2015).

Article  PubMed  Google Scholar 

NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy. Osteoporosis prevention, diagnosis, therapy. JAMA 285, 785–795 (2001).

Article  Google Scholar 

Bergen, D. J. M. et al. High bone mass disorders: new insights from connecting the clinic and the bench. J. Bone Miner. Res. 38, 229–247 (2020).

Article  Google Scholar 

Whyte, M. P. Misinterpretation of osteodensitometry with high bone density: BMD Z ≥+2.5 is not “normal”. J. Clin. Densitom. 8, 1–6 (2005).

Article  PubMed  Google Scholar 

Pocock, N. A. et al. Genetic determinants of bone mass in adults. A twin study. J. Clin. Invest. 80, 706–710 (1987).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Morris, J. A. et al. An atlas of genetic influences on osteoporosis in humans and mice. Nat. Genet. 51, 258–266 (2019).

Article  CAS  PubMed  Google Scholar 

Unger, S. et al. Nosology of genetic skeletal disorders: 2023 revision. Am. J. Med. Genet. A 191, 1164–1209 (2023).

Article  PubMed  PubMed Central  Google Scholar 

Huybrechts, Y., Mortier, G., Boudin, E. & Van Hul, W. WNT signaling and bone: lessons from skeletal dysplasias and disorders. Front. Endocrinol.11, 165 (2020).

Article  Google Scholar 

Wehrli, M. et al. arrow encodes an LDL-receptor-related protein essential for wingless signalling. Nature 407, 527–530 (2000).

Article  CAS  PubMed  Google Scholar 

Bhanot, P. et al. A new member of the frizzled family from Drosophila functions as a wingless receptor. Nature 382, 225–230 (1996).

Article  CAS  PubMed  Google Scholar 

Nampoothiri, S. et al. Ptosis as a unique hallmark for autosomal recessive WNT1-associated osteogenesis imperfecta. Am. J. Med. Genet. A 179, 908–914 (2019).

Article  CAS  PubMed  Google Scholar 

Laine, C. M. et al. WNT1 mutations in early-onset osteoporosis and osteogenesis imperfecta. N. Engl. J. Med. 368, 1809–1816 (2013).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wang, F. et al. Mesenchymal cell-derived juxtacrine wnt1 signaling regulates osteoblast activity and osteoclast differentiation. J. Bone Miner. Res. 34, 1129–1142 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Keupp, K. et al. Mutations in WNT1 cause different forms of bone fragility. Am. J. Hum. Genet. 92, 565–574 (2013).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Beighton, P., Barnard, A., Hamersma, H. & van der Wouden, A. The syndromic status of sclerosteosis and van Buchem disease. Clin. Genet. 25, 175–181 (1984).

Article  CAS  PubMed  Google Scholar 

Brunkow, M. E. et al. Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein. Am. J. Hum. Genet. 68, 577–589 (2001).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Li, X. et al. Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling. J. Biol. Chem. 280, 19883–19887 (2005).

Article  CAS  PubMed  Google Scholar 

Leupin, O. et al. Bone overgrowth-associated mutations in the LRP4 gene impair sclerostin facilitator function. J. Biol. Chem. 286, 19489–19500 (2011).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Loots, G. G. et al. Genomic deletion of a long-range bone enhancer misregulates sclerostin in Van Buchem disease. Genome Res. 15, 928–935 (2005).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kim, S. J. et al. Identification of signal peptide domain SOST mutations in autosomal dominant craniodiaphyseal dysplasia. Hum. Genet. 129, 497–502 (2011).

Article  CAS  PubMed  Google Scholar 

Kiper, P. O. S. et al. Cortical-bone fragility — insights from sFRP4 deficiency in Pyle’s disease. N. Engl. J. Med. 374, 2553–2562 (2016).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sowińska-Seidler, A. et al. The first report of biallelic missense mutations in the SFRP4 gene causing Pyle disease in two siblings. Front. Genet. 11, 593407 (2020).

Article  PubMed  PubMed Central  Google Scholar 

Gong, Y. et al. LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell 107, 513–523 (2001).

Article  CAS  PubMed  Google Scholar 

Balemans, W. & Van Hul, W. The genetics of low-density lipoprotein receptor-related protein 5 in bone: a story of extremes. Endocrinology 148, 2622–2629 (2007).

Article  CAS  PubMed  Google Scholar 

Balemans, W. et al. The binding between sclerostin and LRP5 is altered by DKK1 and by high-bone mass LRP5 mutations. Calcif. Tissue Int. 82, 445–453 (2008).

Article  CAS  PubMed  Google Scholar 

Whyte, M. P. et al. New explanation for autosomal dominant high bone mass: mutation of low-density lipoprotein receptor-related protein 6. Bone 127, 228–243 (2019).

Article  CAS  PubMed  Google Scholar 

Little, R. D. et al. A mutation in the LDL receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait. Am. J. Hum. Genet. 70, 11–19 (2002).

Article  CAS  PubMed  Google Scholar 

Cheng, Z. et al. Crystal structures of the extracellular domain of LRP6 and its complex with DKK1. Nat. Struct. Mol. Biol. 18, 1204–1210 (2011).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ohkawara, B. et al. LRP4 third β-propeller domain mutations cause novel congenital myasthenia by compromising agrin-mediated MuSK signaling in a position-specific manner. Hum. Mol. Genet. 23, 1856–1868 (2014).

Article  CAS  PubMed  Google Scholar 

Huybrechts, Y. et al. Identification of compound heterozygous variants in LRP4 demonstrates that a pathogenic variant outside the third β-propeller domain can cause sclerosteosis. Genes 13, 80 (2021).

Article  PubMed  PubMed Central  Google Scholar 

Orford, K., Crockett, C., Jensen, J. P., Weissman, A. M. & Byers, S. W. Serine phosphorylation-regulated ubiquitination and degradation of β-catenin. J. Biol. Chem. 272, 24735–24738 (1997).

Article  CAS  PubMed  Google Scholar 

Comai, G. et al. Genetic and molecular insights into genotype-phenotype relationships in osteopathia striata with cranial sclerosis (OSCS) through the analysis of novel mouse Wtx mutant alleles. J. Bone Miner. Res. 33, 875–887 (2018).

Article  CAS  PubMed  Google Scholar 

Comments (0)

No login
gif