WNT1 Mutations in Early-Onset Osteoporosis and Osteogenesis Imperfecta

Laine, Christine M.Gothenburg University,Göteborgs universitet,Institutionen för medicin,Institute of Medicine (author)

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(star). 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.

Joeng, K. S. (author)
Campeau, P. M. (author)
Kiviranta, R. (author)
Tarkkonen, K. (author)
Grover, M. (author)
Lu, J. T. (author)
Pekkinen, M. (author)
Wessman, M. (author)
Heino, T. J. (author)
Nieminen-Pihala, V. (author)
Aronen, M. (author)
Laine, TeroGothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för ortopedi,Institute of Clinical Sciences, Department of Orthopaedics (author)
Kroger, H. (author)
Cole, W. G. (author)
Lehesjoki, A. E. (author)
Nevarez, L. (author)
Krakow, D. (author)
Curry, C. J. R. (author)
Cohn, D. H. (author)
Gibbs, R. A. (author)
Lee, B. H. (author)
Makitie, O.Karolinska Institutet (author)
Göteborgs universitetInstitutionen för medicin (creator_code:org_t)

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