{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Ohkawara B"],"funding":["NINDS NIH HHS"],"pagination":["1856-68"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3943522"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["23(7)"],"pubmed_abstract":["Congenital myasthenic syndromes (CMS) are heterogeneous disorders in which the safety margin of neuromuscular transmission is compromised by one or more specific mechanisms. Using Sanger and exome sequencing in a CMS patient, we identified two heteroallelic mutations, p.Glu1233Lys and p.Arg1277His, in LRP4 coding for the postsynaptic low-density lipoprotein receptor-related protein 4. LRP4, expressed on the surface of the postsynaptic membrane of the neuromuscular junction, is a receptor for neurally secreted agrin, and LRP4 bound by agrin activates MuSK. Activated MuSK in concert with Dok-7 stimulates rapsyn to concentrate and anchor AChR on the postsynaptic membrane and interacts with other proteins implicated in the assembly and maintenance of the neuromuscular junction. LRP4 also funct"],"journal":["Human molecular genetics"],"pubmed_title":["LRP4 third β-propeller domain mutations cause novel congenital myasthenia by compromising agrin-mediated MuSK signaling in a position-specific manner."],"pmcid":["PMC3943522"],"funding_grant_id":["R01 NS006277","NS6277","R56 NS006277"],"pubmed_authors":["Milone M","Nakata T","Engel AG","Ohkawara B","Ito K","Asai N","Ito Y","Masuda A","Ohno K","Ito M","Cabrera-Serrano M"],"additional_accession":[]},"is_claimable":false,"name":"LRP4 third β-propeller domain mutations cause novel congenital myasthenia by compromising agrin-mediated MuSK signaling in a position-specific manner.","description":"Congenital myasthenic syndromes (CMS) are heterogeneous disorders in which the safety margin of neuromuscular transmission is compromised by one or more specific mechanisms. Using Sanger and exome sequencing in a CMS patient, we identified two heteroallelic mutations, p.Glu1233Lys and p.Arg1277His, in LRP4 coding for the postsynaptic low-density lipoprotein receptor-related protein 4. LRP4, expressed on the surface of the postsynaptic membrane of the neuromuscular junction, is a receptor for neurally secreted agrin, and LRP4 bound by agrin activates MuSK. Activated MuSK in concert with Dok-7 stimulates rapsyn to concentrate and anchor AChR on the postsynaptic membrane and interacts with other proteins implicated in the assembly and maintenance of the neuromuscular junction. LRP4 also funct","dates":{"release":"2014-01-01T00:00:00Z","publication":"2014 Apr","modification":"2026-04-16T01:17:31.673Z","creation":"2019-03-27T01:22:43Z"},"accession":"S-EPMC3943522","cross_references":{"pubmed":["24234652"],"doi":["10.1093/hmg/ddt578"]}}