@article {695,
	title = {Dominant-negative SOX9 mutations in campomelic dysplasia.},
	journal = {Hum Mutat},
	volume = {40},
	year = {2019},
	month = {2019 12},
	pages = {2344-2352},
	abstract = {<p>Campomelic dysplasia (CD) is an autosomal dominant, perinatal lethal skeletal dysplasia characterized by a small chest and short long bones with bowing of the lower extremities. CD is the result of heterozygosity for mutations in the gene encoding the chondrogenesis master regulator, SOX9. Loss-of-function mutations have been identified in most CD cases so it has been assumed that the disease results from haploinsufficiency for SOX9. Here, we identified distal truncating SOX9 mutations in four unrelated CD cases. The mutations all leave the dimerization and DNA-binding domains intact and cultured chondrocytes from three of the four cases synthesized truncated SOX9. Relative to CD resulting from haploinsufficiency, there was decreased transactivation activity toward a major transcriptional target, COL2A1, consistent with the mutations exerting a dominant-negative effect. For one of the cases, the phenotypic consequence was a very severe form of CD, with a pronounced effect on vertebral and limb development. The data identify a novel molecular mechanism of disease in CD in which the truncated protein leads to a distinct and more significant effect on SOX9 function.</p>},
	issn = {1098-1004},
	doi = {10.1002/humu.23888},
	author = {Csukasi, Fabiana and Duran, Ivan and Zhang, Wenjuan and Martin, Jorge H and Barad, Maya and Bamshad, Michael and Weis, Mary Ann and Eyre, David and Krakow, Deborah and Cohn, Daniel H}
}
@article {18,
	title = {Destabilization of the IFT-B cilia core complex due to mutations in IFT81 causes a Spectrum of Short-Rib Polydactyly Syndrome.},
	journal = {Sci Rep},
	volume = {6},
	year = {2016},
	month = {2016 Sep 26},
	pages = {34232},
	abstract = {<p>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.</p>},
	issn = {2045-2322},
	doi = {10.1038/srep34232},
	author = {Duran, Ivan and Taylor, S Paige and Zhang, Wenjuan and Martin, Jorge and Forlenza, Kimberly N and Spiro, Rhonda P and Nickerson, Deborah A and Bamshad, Michael and Cohn, Daniel H and Krakow, Deborah}
}
