{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Caparros-Martin JA"],"funding":["NHLBI NIH HHS","Medical Research Council"],"pagination":["4126-37"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4560068"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["24(14)"],"pubmed_abstract":["Most patients with Ellis-van Creveld syndrome (EvC) are identified with pathogenic changes in EVC or EVC2, however further genetic heterogeneity has been suggested. In this report we describe pathogenic splicing variants in WDR35, encoding retrograde intraflagellar transport protein 121 (IFT121), in three families with a clinical diagnosis of EvC but having a distinctive phenotype. To understand why WDR35 variants result in EvC, we analysed EVC, EVC2 and Smoothened (SMO) in IFT-A deficient cells. We found that the three proteins failed to localize to Wdr35(-/-) cilia, but not to the cilium of the IFT retrograde motor mutant Dync2h1(-/-), indicating that IFT121 is specifically required for their entry into the ciliary compartment. Furthermore expression of Wdr35 disease cDNAs in Wdr35(-/-) "],"journal":["Human molecular genetics"],"pubmed_title":["Specific variants in WDR35 cause a distinctive form of Ellis-van Creveld syndrome by disrupting the recruitment of the EvC complex and SMO into the cilium."],"pmcid":["PMC4560068"],"funding_grant_id":["RC2 HL102926","RC2 HL102925","UC2 HL102923","RC2 HL102924","RC2 HL102923","UC2 HL102924","UC2 HL102925","HL-103010","UC2 HL102926","RC2 HL103010","HL-102925","HL-102926","MC_UU_12018/26","HL-102923","HL-102924","UC2 HL103010"],"pubmed_authors":["Caparros-Martin JA","Heath KE","Nevado J","Temtamy S","Alessandri JL","Dallapiccola B","Cartault F","Digilio MC","Lapunzina P","Vazquez L","Mill P","Aglan M","Goodship JA","Valencia M","Mehrez M","De Luca A","Ruiz-Perez VL","Otaify GA","Rueda-Arenas I"],"additional_accession":[]},"is_claimable":false,"name":"Specific variants in WDR35 cause a distinctive form of Ellis-van Creveld syndrome by disrupting the recruitment of the EvC complex and SMO into the cilium.","description":"Most patients with Ellis-van Creveld syndrome (EvC) are identified with pathogenic changes in EVC or EVC2, however further genetic heterogeneity has been suggested. In this report we describe pathogenic splicing variants in WDR35, encoding retrograde intraflagellar transport protein 121 (IFT121), in three families with a clinical diagnosis of EvC but having a distinctive phenotype. To understand why WDR35 variants result in EvC, we analysed EVC, EVC2 and Smoothened (SMO) in IFT-A deficient cells. We found that the three proteins failed to localize to Wdr35(-/-) cilia, but not to the cilium of the IFT retrograde motor mutant Dync2h1(-/-), indicating that IFT121 is specifically required for their entry into the ciliary compartment. Furthermore expression of Wdr35 disease cDNAs in Wdr35(-/-) ","dates":{"release":"2015-01-01T00:00:00Z","publication":"2015 Jul","modification":"2026-05-29T23:08:33.815Z","creation":"2019-03-27T01:57:51Z"},"accession":"S-EPMC4560068","cross_references":{"pubmed":["25908617"],"doi":["10.1093/hmg/ddv152"]}}