Destabilization of the IFT-B cilia core complex due to mutations in IFT81 causes a Spectrum of Short-Rib Polydactyly Syndrome
Year: 2016
Type: article
Abstract: Short-rib polydactyly syndromes (SRPS) and Asphyxiating thoracic dystrophy (ATD) or Jeune Syndrome are recessively inherited skeletal ciliopathies characterized by profound skeletal abnormalities and are frequently associated with polydactyly and multiorgan system involvement. SRPS are produced by mutations in genes that participate in the formation and function of primary cilia and usually result from disruption of retrograde intraflagellar (IFT) transport of the cilium. Herein we describe a new spectrum of SRPS caused by mutations in the gene IFT81, a key component of the IFT-B complex essential for anterograde transport. In mutant chondrocytes, the mutations led to low levels of IFT81 and mutant cells produced elongated cilia, had altered hedgehog signaling, had increased post-translation modification of tubulin, and showed evidence of destabilization of additional anterograde transport complex components. These findings demonstrate the importance of IFT81 in the skeleton, its role in the anterograde transport complex, and expand the number of loci associated with SRPS.
Source: Scientific Reports
DOI: 10.1038/srep34232
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,690
Funders: March of Dimes Foundation, University of Washington, National Institutes of Health, National Human Genome Research Institute, National Institute of General Medical Sciences, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute of Dental and Craniofacial Research, National Center for Advancing Translational Sciences, Clinical and Translational Science Institute, University of California, Los Angeles
Awards: G1068064772, G1545794908, G2014386550, Mechanism of Action of Dynactin, UCLA Clinical and Translational Science Institute, Exome sequencing in the skeletal dysplasias, UW Center for Mendelian Genomics, Unraveling the mechanisms of prenatal-onset disorders affecting the skeleton, Short-rib polydactyly and the skeletal ciliopathies, UW Center for Mendelian Genomics, G9000345790
OpenAlex ID: W2523873064