Article ; Online: Novel variant in LRP6 associated with unusual and severe clinical presentation: Case report.
2024 Volume 105, Issue 6, Page(s) 666–670
Abstract: Low-density lipoprotein receptor-related protein 6 (LRP6) is a co-receptor of the Wnt signaling pathway, which plays an essential role in various biological activities during embryonic and postnatal development. LRP6 is exceptionally associated with rare ...
Abstract | Low-density lipoprotein receptor-related protein 6 (LRP6) is a co-receptor of the Wnt signaling pathway, which plays an essential role in various biological activities during embryonic and postnatal development. LRP6 is exceptionally associated with rare diseases and always with autosomal dominant inheritance. Here we report a familial phenotype of high bone mass associated with skeletal anomalies and oligodontia but also persistent left superior vena cava, inguinal hernia, hepatic cysts, abnormal posterior fossa and genital malformations. Molecular analysis revealed a novel heterozygous variant, NM_002336.2: c.724T>C, p.(Trp242Arg), in affected individuals. This variant is located in the first β-propellant motif of LRP6, to which sclerostin (SOST) and dickkopf1 (DKK1), two LRP6 co-receptor inhibitors and various Wnt ligands bind. According to the literature and integrating data from structural analysis, this variant distorts the binding of SOST and DKK1, thus leading to overactivation of Wnt signaling pathways involved in osteoblast differentiation. This novel heterozygous variant in LRP6 underlies the role of LRP6 in skeletal and dental disorders as well as, probably, cardiac, cerebral and genital developments. |
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MeSH term(s) | Humans ; Low Density Lipoprotein Receptor-Related Protein-6/genetics ; Male ; Female ; Phenotype ; Mutation/genetics ; Wnt Signaling Pathway/genetics ; Pedigree ; Intercellular Signaling Peptides and Proteins/genetics ; Adaptor Proteins, Signal Transducing/genetics |
Chemical Substances | Low Density Lipoprotein Receptor-Related Protein-6 ; LRP6 protein, human ; DKK1 protein, human ; Intercellular Signaling Peptides and Proteins ; Adaptor Proteins, Signal Transducing |
Language | English |
Publishing date | 2024-02-22 |
Publishing country | Denmark |
Document type | Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't |
ZDB-ID | 221209-2 |
ISSN | 1399-0004 ; 0009-9163 |
ISSN (online) | 1399-0004 |
ISSN | 0009-9163 |
DOI | 10.1111/cge.14501 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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