A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
WNT1 Mutations in Early-Onset Osteoporosis and Osteogenesis Imperfecta
Tekijät: 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 CJR, Cohn DH, Gibbs RA, Lee BH, Makitie O
Kustantaja: MASSACHUSETTS MEDICAL SOC
Julkaisuvuosi: 2013
Journal: New England Journal of Medicine
Tietokannassa oleva lehden nimi: NEW ENGLAND JOURNAL OF MEDICINE
Lehden akronyymi: NEW ENGL J MED
Numero sarjassa: 19
Vuosikerta: 368
Numero: 19
Aloitussivu: 1809
Lopetussivu: 1816
Sivujen määrä: 8
ISSN: 0028-4793
DOI: https://doi.org/10.1056/NEJMoa1215458
Tiivistelmä
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.
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.
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