کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5891850 1153281 2011 4 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Identification of the first deletion in the LRP5 gene in a patient with Autosomal Dominant Osteopetrosis type I
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شناسی تکاملی
پیش نمایش صفحه اول مقاله
Identification of the first deletion in the LRP5 gene in a patient with Autosomal Dominant Osteopetrosis type I
چکیده انگلیسی

In the last decade, the low-density lipoprotein receptor-related protein 5 (LRP5) gene, coding for a coreceptor in the canonical Wnt signalling pathway, has been shown to play an important role in regulating bone mass and to be involved in the pathogenesis of several bone disorders. Here we describe a patient who presented with a clinical picture of Autosomal Dominant Osteopetrosis type I (ADO I), in whom we could identify the first deletion in the LRP5 gene causing increased bone mass. This mutation caused the in-frame deletion of two amino acids in the fourth blade of the first propeller of the protein, namely the highly conserved glycine at position 171 and the following glutamate residue. In vitro studies suggested that the pathogenic effect of this novel mutation could be due to a decreased inhibition of Wnt signalling by the antagonistic proteins sclerostin and Dickkopf-1, encoded respectively by the SOST and DKK1 genes, in the presence of mutated LRP5. Our results highlight an increasing molecular heterogeneity in LRP5-related bone diseases.

► We report the first deletion of 2 amino acid residues in LRP5 in an ADO I patient. ► This suggests an increasing molecular heterogeneity in LRP5-related bone diseases. ► This deletion causes decreased inhibition of Wnt signalling by sclerostin and DKK1. ► ADO I and ADO II are clinically and molecularly distinct entities. ► No impairment of the immune system has been documented in ADO I patients.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bone - Volume 49, Issue 3, September 2011, Pages 568-571
نویسندگان
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