WNT1 mutations in early-onset osteoporosis and osteogenesis imperfecta.
N Engl J Med
; 368(19): 1809-16, 2013 May 09.
Article
em En
| MEDLINE
| ID: mdl-23656646
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.652TâG (p.Cys218Gly). In a separate family with 2 siblings affected by recessive osteogenesis imperfecta, we identified a homozygous nonsense mutation, c.884CâA, 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.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Osteogênese Imperfeita
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Osteoporose
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Proteína Wnt1
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Mutação
Limite:
Adolescent
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Adult
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Aged
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Animals
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Child
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
N Engl J Med
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Finlândia