Rare variations in WNT3A and DKK1 may predispose carriers to primary osteoporosis

Johanna Korvala, Marika Löija, Outi Mäkitie, Etienne Sochett, Harald Jüppner, Dirk Schnabel, Stefano Mora, William G. Cole, Leena Ala-Kokko, Minna Männikkö

Research output: Contribution to journalArticlepeer-review


Childhood-onset primary osteoporosis is manifested as reduced bone mineral density, peripheral fractures and/or vertebral compression fractures. Until now, only mutations in LRP5 have been shown to cause the disorder. Candidate gene analyses were performed on 15 patients with primary osteoporosis and 80 healthy controls using CSGE and sequencing. The genes studied included DKK1, DKK2, WNT3A, WNT10B, AXIN1, SOST, TPH1 and 5- HTR1B. Two rare variants in WNT3A (c.152A > G, p.K51R) and DKK1 (c.359G > T, p.R120L) were identified in two patients and their affected family members, but not in control subjects, suggesting a significance for the skeletal phenotype. The in vitro studies of variants showed reduced signaling activity in p.K51R-Wnt3a, while no differences were observed between the WT and variant forms of DKK1. This study addresses the role of other components of the canonical Wnt signaling pathway besides LRP5 in primary osteoporosis, and putatively associates WNT3A and DKK1 variants with the disorder. Future functional studies are needed to elucidate the functional effects of the variants.

Original languageEnglish
Pages (from-to)515-519
Number of pages5
JournalEuropean Journal of Medical Genetics
Issue number10
Publication statusPublished - Oct 2012


  • Bone
  • DKK1
  • Genetics
  • Osteoporosis
  • WNT3A

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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