{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Huybrechts Y"],"funding":["Research Foundation - Flanders","Methusalem - OEC grant - "GENOMED""],"pagination":["80"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8774882"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["13(1)"],"pubmed_abstract":["Sclerosteosis is a high bone mass disorder, caused by pathogenic variants in the genes encoding sclerostin or LRP4. Both proteins form a complex that strongly inhibits canonical WNT signaling activity, a pathway of major importance in bone formation. So far, all reported disease-causing variants are located in the third β-propeller domain of LRP4, which is essential for the interaction with sclerostin. Here, we report the identification of two compound heterozygous variants, a known p.Arg1170Gln and a novel p.Arg632His variant, in a patient with a sclerosteosis phenotype. Interestingly, the novel variant is located in the first β-propeller domain, which is known to be indispensable for the interaction with agrin. However, using luciferase reporter assays, we demonstrated that both the p.Ar"],"journal":["Genes"],"pubmed_title":["Identification of Compound Heterozygous Variants in LRP4 Demonstrates That a Pathogenic Variant outside the Third β-Propeller Domain Can Cause Sclerosteosis."],"pmcid":["PMC8774882"],"funding_grant_id":["12A3814N","G031915N","FFB190208"],"pubmed_authors":["Bracamonte MS","Hamdy N","Steenackers E","Huybrechts Y","Martinez Diaz-Guerra G","Appelman-Dijkstra NM","Boudin E","Hendrickx G","Van Hul W","Mortier G"],"additional_accession":[]},"is_claimable":false,"name":"Identification of Compound Heterozygous Variants in LRP4 Demonstrates That a Pathogenic Variant outside the Third β-Propeller Domain Can Cause Sclerosteosis.","description":"Sclerosteosis is a high bone mass disorder, caused by pathogenic variants in the genes encoding sclerostin or LRP4. Both proteins form a complex that strongly inhibits canonical WNT signaling activity, a pathway of major importance in bone formation. So far, all reported disease-causing variants are located in the third β-propeller domain of LRP4, which is essential for the interaction with sclerostin. Here, we report the identification of two compound heterozygous variants, a known p.Arg1170Gln and a novel p.Arg632His variant, in a patient with a sclerosteosis phenotype. Interestingly, the novel variant is located in the first β-propeller domain, which is known to be indispensable for the interaction with agrin. However, using luciferase reporter assays, we demonstrated that both the p.Ar","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Dec","modification":"2025-04-04T13:48:17.914Z","creation":"2022-02-11T15:52:18.726Z"},"accession":"S-EPMC8774882","cross_references":{"pubmed":["35052419"],"doi":["10.3390/genes13010080"]}}