title: WNT1 mutations in early-onset osteoporosis and osteogenesis imperfecta.
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.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.
authors: Folkhälsan Institute of Genetics, University of Helsinki, Helsinki, Finland.
authors: Christine M
authors: CM
authors: Laine
authors: Kyu Sang
authors: KS
authors: Joeng
authors: Philippe M
authors: PM
authors: Campeau
authors: Riku
authors: R
authors: Kiviranta
authors: Kati
authors: K
authors: Tarkkonen
authors: Monica
authors: M
authors: Grover
authors: James T
authors: JT
authors: Lu
authors: Minna
authors: M
authors: Pekkinen
authors: Maija
authors: M
authors: Wessman
authors: Terhi J
authors: TJ
authors: Heino
authors: Vappu
authors: V
authors: Nieminen-Pihala
authors: Mira
authors: M
authors: Aronen
authors: Tero
authors: T
authors: Laine
authors: Heikki
authors: H
authors: Kröger
authors: William G
authors: WG
authors: Cole
authors: Anna-Elina
authors: AE
authors: Lehesjoki
authors: Lisette
authors: L
authors: Nevarez
authors: Deborah
authors: D
authors: Krakow
authors: Cynthia J R
authors: CJ
authors: Curry
authors: Daniel H
authors: DH
authors: Cohn
authors: Richard A
authors: RA
authors: Gibbs
authors: Brendan H
authors: BH
authors: Lee
authors: Outi
authors: O
authors: Mäkitie
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000818:Animals; D002648:Child; D005260:Female; D005799:Genes, Dominant; D005808:Genes, Recessive; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D009154:Mutation; D010013:Osteogenesis Imperfecta / Q000235:genetics*; D010024:Osteoporosis / Q000235:genetics*; D010375:Pedigree; D051155:Wnt1 Protein / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: C495247:WNT1 protein, human; D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse
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