Human LRP4 blocking peptide

Cenani-Lenz (C-L) syndrome is characterized by oligosyndactyly, metacarpal synostosis, phalangeal disorganization, and other variable facial and systemic features. Most cases are caused by homozygous and compound heterozygous missense and splice mutations of the LRP4 gene. Currently, the syndrome carries one OMIM number (212780). However, C-L syndrome-like phenotypes as well as other syndactyly disorders with or without metacarpal synostosis/phalangeal disorganization are also known to be associated with specific LRP4 mutations, adenomatous polyposis coli (APC) truncating mutations, genomic rearrangements of the GREM1-FMN1 locus, as well as FMN1 mutations. Surprisingly, patients with C-L syndrome-like phenotype caused by APC truncating mutations have no polyposis despite the increased levels of catenin. The LRP4 and APC proteins act on the WNT (wingless-type integration site family) canonical pathway, whereas the GREM-1 and FMN1 proteins act on the bone morphogenetic protein (BMP) pathway. In this review, we discuss the different mutations associated with C-L syndrome, classify its clinical features, review familial adenomatous polyposis caused by truncating APC mutations and compare these mutations to the splicing APC mutation associated with syndactyly, and finally, explore the pathophysiology through a review of the cross talks between the WNT canonical and the BMP antagonistic pathways.

Muscle-specific tyrosine kinase (MuSK) antibodies are detected in a proportion of myasthenia gravis (MG) patients who are negative for acetylcholine receptor (AChR) antibodies and have prominent bulbar weakness and crises. In the MuSK ectodomains, the immunoglobulin-like 1 and 2 domains (Ig1/2) mediate the agrin-Lrp4-MuSK signaling and the cysteine-rich domain (CRD) mediates the Wnt-MuSK-Dishevelled signaling; both contribute to AChR clustering. Immunoblotting against recombinant proteins showed MuSK Ig1/2 antibodies in 33 anti-AChR-negative MG patients; 10 patients of them (30%) were additionally positive for MuSK CRD antibodies. The result suggests that MuSK antibodies have heterogeneity in their binding to functional domains of MuSK. (C) 2012 Elsevier B.V. All rights reserved.