Journal article
Mutations in CDC45, Encoding an Essential Component of the Pre-initiation Complex, Cause Meier-Gorlin Syndrome and Craniosynostosis
AL Fenwick, M Kliszczak, F Cooper, J Murray, L Sanchez-Pulido, SRF Twigg, A Goriely, SJ McGowan, KA Miller, IB Taylor, C Logan, S Bozdogan, S Danda, J Dixon, SM Elsayed, E Elsobky, A Gardham, MJV Hoffer, M Koopmans, DM McDonald-McGinn Show all
American Journal of Human Genetics | CELL PRESS | Published : 2016
Abstract
DNA replication precisely duplicates the genome to ensure stable inheritance of genetic information. Impaired licensing of origins of replication during the G1 phase of the cell cycle has been implicated in Meier-Gorlin syndrome (MGS), a disorder defined by the triad of short stature, microtia, and a/hypoplastic patellae. Biallelic partial loss-of-function mutations in multiple components of the pre-replication complex (preRC; ORC1, ORC4, ORC6, CDT1, or CDC6) as well as de novo stabilizing mutations in the licensing inhibitor, GMNN, cause MGS. Here we report the identification of mutations in CDC45 in 15 affected individuals from 12 families with MGS and/or craniosynostosis. CDC45 encodes a ..
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Awarded by Department of Health and Social Care
Funding Acknowledgements
We thank the families and clinicians for their participation, the IGMM core sequencing service, staff at the High-Throughput Genomics facility at the Wellcome Trust Centre for Human Genetics (Oxford) for Illumina sequencing, Tim Forshew and Francesco Marass for primer design, and Sue Butler, John Frankland, and Tim Rostron for help with cell culture and DNA sequencing. This work was supported by funding from the Medical Research Council (MRC) (A.P.J., L.S.-P., C.P.P., W.N.) and through the WIMM Strategic Alliance (G0902418 and MC_UU_12025), the European Research Council (ERC, 281847) (A.P.J.), the Lister Institute for Preventative Medicine (A.P.J.), Medical Research Scotland (L.S.B.), Royal Society of New Zealand Rutherford Discovery Fellowship (L.S.B.), the Department of Health, UK, Quality, Improvement, Development and Initiative Scheme (QIDIS) (A.O.M.W.), Newlife Foundation for Disabled Children (SG/14-15/10 to A.O.M.W.), National Institute for Health Research (NIHR) Oxford Biomedical Research Centre Programme (A.O.M.W.), and the Wellcome Trust (Project Grant 093329 to A.O.M.W. and S.R.F.T.; Investigator Award 102731 to A.O.M.W.).