[HTML][HTML] WNT1 Mutations in Early-Onset Osteoporosis and Osteogenesis Imperfecta

CM Laine, KS Joeng, PM Campeau… - … England Journal of …, 2013 - Mass Medical Soc
CM Laine, KS Joeng, PM Campeau, R Kiviranta, K Tarkkonen, M Grover, JT Lu, M Pekkinen…
New England Journal of Medicine, 2013Mass Medical Soc
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 …
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.
The New England Journal Of Medicine