Journal article
Human and mouse mutations in WDR35 cause short-rib polydactyly syndromes due to abnormal ciliogenesis
P Mill, PJ Lockhart, E Fitzpatrick, HS Mountford, EA Hall, MAM Reijns, M Keighren, M Bahlo, CJ Bromhead, P Budd, S Aftimos, MB Delatycki, R Savarirayan, IJ Jackson, DJ Amor
American Journal of Human Genetics | Published : 2011
Abstract
Defects in cilia formation and function result in a range of human skeletal and visceral abnormalities. Mutations in several genes have been identified to cause a proportion of these disorders, some of which display genetic (locus) heterogeneity. Mouse models are valuable for dissecting the function of these genes, as well as for more detailed analysis of the underlying developmental defects. The short-rib polydactyly (SRP) group of disorders are among the most severe human phenotypes caused by cilia dysfunction. We mapped the disease locus from two siblings affected by a severe form of SRP to 2p24, where we identified an in-frame homozygous deletion of exon 5 in WDR35. We subsequently found..
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Awarded by Natural Sciences and Engineering Research Council of Canada
Funding Acknowledgements
We thank K. Pope (Clinical Research Coordinator, MCRI) and the families involved in this research. We thank I. Algianis, E. Maher, and C. Patel for sharing clinical samples for WDR35 screening. We are grateful to P. Perry and M. Pearson for imaging assistance. We thank D. FitzPatrick, A. Jackson, and T. Kunath for critical comments on the manuscript. This work was funded by the Medical Research Council (UK) and the National Health and Medical Research Council Australia (program grant 490037). Support to P.M. was provided by fellowships from the National Sciences and Engineering Research Council of Canada and the Caledonian Research Foundation. P.J.L. was supported by a National Health and Medical Research Council Australia RD Wright Fellowship (334346).