@article {931,
	title = {Mutations in GRK2 cause Jeune syndrome by impairing Hedgehog and canonical Wnt signaling.},
	journal = {EMBO Mol Med},
	volume = {12},
	year = {2020},
	month = {2020 11 06},
	pages = {e11739},
	abstract = {<p>Mutations in genes affecting primary cilia cause ciliopathies, a diverse group of disorders often affecting skeletal development. This includes Jeune syndrome or asphyxiating thoracic dystrophy (ATD), an autosomal recessive skeletal disorder. Unraveling the responsible molecular pathology helps illuminate mechanisms responsible for functional primary cilia. We identified two families with ATD caused by loss-of-function mutations in the gene encoding adrenergic receptor kinase 1 (ADRBK1 or GRK2). GRK2 cells from an affected individual homozygous for the p.R158* mutation resulted in loss of GRK2, and disrupted chondrocyte growth and differentiation in the cartilage growth plate. GRK2 null cells displayed normal cilia morphology, yet loss of GRK2 compromised cilia-based signaling of Hedgehog (Hh) pathway. Canonical Wnt signaling was also impaired, manifested as a failure to respond to Wnt ligand due to impaired phosphorylation of the Wnt co-receptor LRP6. We have identified GRK2 as an essential regulator of skeletogenesis and demonstrate how both Hh and Wnt signaling mechanistically contribute to skeletal ciliopathies.</p>},
	issn = {1757-4684},
	doi = {10.15252/emmm.201911739},
	author = {Bosakova, Michaela and AbrAHm, Sara P and Nita, Alexandru and Hruba, Eva and Buchtova, Marcela and Taylor, S Paige and Duran, Ivan and Martin, Jorge and Svozilova, Katerina and Barta, Tomas and Varecha, Miroslav and Balek, Lukas and Kohoutek, Jiri and Radaszkiewicz, Tomasz and Pusapati, Ganesh V and Bryja, Vitezslav and Rush, Eric T and Thiffault, Isabelle and Nickerson, Deborah A and Bamshad, Michael J and Rohatgi, Rajat and Cohn, Daniel H and Krakow, Deborah and Krejci, Pavel}
}
@article {343,
	title = {An inactivating mutation in intestinal cell kinase, ICK, impairs hedgehog signalling and causes short rib-polydactyly syndrome.},
	journal = {Hum Mol Genet},
	volume = {25},
	year = {2016},
	month = {2016 09 15},
	pages = {3998-4011},
	abstract = {<p>The short rib polydactyly syndromes (SRPS) are a group of recessively inherited, perinatal-lethal skeletal disorders primarily characterized by short ribs, shortened long bones, varying types of polydactyly and concomitant visceral abnormalities. Mutations in several genes affecting cilia function cause SRPS, revealing a role for cilia function in skeletal development. To identify additional SRPS genes and discover novel ciliary molecules required for normal skeletogenesis, we performed exome sequencing in a cohort of patients and identified homozygosity for a missense mutation, p.E80K, in Intestinal Cell Kinase, ICK, in one SRPS family. The p.E80K mutation abolished serine/threonine kinase activity, resulting in altered ICK subcellular and ciliary localization, increased cilia length, aberrant cartilage growth plate structure, defective Hedgehog and altered ERK signalling. These data identify ICK as an SRPS-associated gene and reveal that abnormalities in signalling pathways contribute to defective skeletogenesis.</p>},
	keywords = {Abnormalities, Multiple, Cilia, Exome, Female, Hedgehog Proteins, Humans, Infant, MAP Kinase Signaling System, Pedigree, Pregnancy, Protein-Serine-Threonine Kinases, Sequence Analysis, DNA, Short Rib-Polydactyly Syndrome, Signal Transduction, Skeleton},
	issn = {1460-2083},
	doi = {10.1093/hmg/ddw240},
	author = {Paige Taylor, S and Kunova Bosakova, Michaela and Varecha, Miroslav and Balek, Lukas and Barta, Tomas and Trantirek, Lukas and Jelinkova, Iva and Duran, Ivan and Vesela, Iva and Forlenza, Kimberly N and Martin, Jorge H and Hampl, Ales and Bamshad, Michael and Nickerson, Deborah and Jaworski, Margie L and Song, Jieun and Ko, Hyuk Wan and Cohn, Daniel H and Krakow, Deborah and Krejci, Pavel}
}
