کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2811426 1569227 2013 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Mutations in WNT1 Cause Different Forms of Bone Fragility
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی ژنتیک
پیش نمایش صفحه اول مقاله
Mutations in WNT1 Cause Different Forms of Bone Fragility
چکیده انگلیسی

We report that hypofunctional alleles of WNT1 cause autosomal-recessive osteogenesis imperfecta, a congenital disorder characterized by reduced bone mass and recurrent fractures. In consanguineous families, we identified five homozygous mutations in WNT1: one frameshift mutation, two missense mutations, one splice-site mutation, and one nonsense mutation. In addition, in a family affected by dominantly inherited early-onset osteoporosis, a heterozygous WNT1 missense mutation was identified in affected individuals. Initial functional analysis revealed that altered WNT1 proteins fail to activate canonical LRP5-mediated WNT-regulated β-catenin signaling. Furthermore, osteoblasts cultured in vitro showed enhanced Wnt1 expression with advancing differentiation, indicating a role of WNT1 in osteoblast function and bone development. Our finding that homozygous and heterozygous variants in WNT1 predispose to low-bone-mass phenotypes might advance the development of more effective therapeutic strategies for congenital forms of bone fragility, as well as for common forms of age-related osteoporosis.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 92, Issue 4, 4 April 2013, Pages 565–574
نویسندگان
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