WNT1 mutations in early-onset osteoporosis and osteogenesis imperfecta.
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Laine CM, Joeng KS, Campeau PM, Kiviranta R, Tarkkonen K, Grover M, Lu JT, Pekkinen M, Wessman M, Heino TJ, Nieminen-Pihala V, Aronen M, Laine T, Kroger H, Cole WG, Lehesjoki AE, Nevarez L, Krakow D, Curry CJ, Cohn DH, Gibbs RA, Lee BH, Makitie O
WNT1 mutations in early-onset osteoporosis and osteogenesis imperfecta.
N Engl J Med. 2013 May 9;368(19):1809-16. doi: 10.1056/NEJMoa1215458.
- PubMed ID
- 23656646 [ View in PubMed]
- Abstract
This report identifies human skeletal diseases associated with mutations in WNT1. In 10 family members with dominantly inherited, early-onset osteoporosis, we identified a heterozygous missense mutation in WNT1, c.652T-->G (p.Cys218Gly). In a separate family with 2 siblings affected by recessive osteogenesis imperfecta, we identified a homozygous nonsense mutation, c.884C-->A, p.Ser295*. In vitro, aberrant forms of the WNT1 protein showed impaired capacity to induce canonical WNT signaling, their target genes, and mineralization. In mice, Wnt1 was clearly expressed in bone marrow, especially in B-cell lineage and hematopoietic progenitors; lineage tracing identified the expression of the gene in a subset of osteocytes, suggesting the presence of altered cross-talk in WNT signaling between the hematopoietic and osteoblastic lineage cells in these diseases.