Destabilization of the IFT-B cilia core complex due to mutations in IFT81 causes a Spectrum of Short-Rib Polydactyly Syndrome.

TitleDestabilization of the IFT-B cilia core complex due to mutations in IFT81 causes a Spectrum of Short-Rib Polydactyly Syndrome.
Publication TypeJournal Article
Year of Publication2016
AuthorsDuran, I, S Taylor, P, Zhang, W, Martin, J, Forlenza, KN, Spiro, RP, Nickerson, DA, Bamshad, M, Cohn, DH, Krakow, D
JournalSci Rep
Volume6
Pagination34232
Date Published2016 Sep 26
ISSN2045-2322
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.

DOI10.1038/srep34232
Alternate JournalSci Rep
PubMed ID27666822
PubMed Central IDPMC5035930
Grant ListR01 DE019567 / DE / NIDCR NIH HHS / United States
U54 HG006493 / HG / NHGRI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
UM1 HG006493 / HG / NHGRI NIH HHS / United States
R01 AR066124 / AR / NIAMS NIH HHS / United States
R01 AR062651 / AR / NIAMS NIH HHS / United States
R01 GM102347 / GM / NIGMS NIH HHS / United States