Molecular and Clinical Analyses of Greig Cephalopolysyndactyly and Pallister-Hall Syndromes: Robust Phenotype Prediction from the Type and Position of.

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Molecular and Clinical Analyses of Greig Cephalopolysyndactyly and Pallister-Hall Syndromes: Robust Phenotype Prediction from the Type and Position of GLI3 Mutations Jennifer J. Johnston, Isabelle Olivos-Glander, Christina Killoran, Emma Elson, Joyce T. Turner, Kathryn F. Peters, Margaret H. Abbott, David J. Aughton, Arthur S. Aylsworth, Michael J. Bamshad, Carol Booth, Cynthia J. Curry, Albert David, Mary Beth Dinulos, David B. Flannery, Michelle A. Fox, John M. Graham, Dorothy K. Grange, Alan E. Guttmacher, Mark C. Hannibal, Wolfram Henn, RaoulC.M. Hennekam, Lewis B. Holmes, H. Eugene Hoyme, Kathleen A. Leppig, Angela E. Lin, Patrick MacLeod, David K. Manchester, Carlo Marcelis, Laura Mazzanti, Emma McCann, Marie T. McDonald, Nancy J. Mendelsohn, John B. Moeschler, Billur Moghaddam, Giovanni Neri, Ruth Newbury-Ecob, Roberta A. Pagon, John A. Phillips III, Laurie S. Sadler, Joan M. Stoler, David Tilstra, Catherine M. Walsh Vockley, Elaine H. Zackai, Touran M. Zadeh, Louise Brueton, Graeme Charles M. Black, Leslie G. Biesecker The American Journal of Human Genetics Volume 76, Issue 4, Pages 609-622 (April 2005) DOI: 10.1086/429346 Copyright © 2005 The American Society of Human Genetics Terms and Conditions

Figure 1 Flow chart showing numbers of patients included in each part of the study. Notice that, for completeness, data for all patients except those with large deletions are included in tables 1 and 2. (Some of the data have been published elsewhere, as noted.) The American Journal of Human Genetics 2005 76, 609-622DOI: (10.1086/429346) Copyright © 2005 The American Society of Human Genetics Terms and Conditions

Figure 2 Type and distribution of GLI3 mutations described for patients with PHS and GCPS. A, Mutation spectrum. No mutations of the following types have been described for patients with PHS: small in-frame deletions (IFD), translocations (Trans), large deletions (L Del), exonic deletions or duplications (Exon), and missense mutations (Miss). The correlation of mutation type and phenotype is statistically significant (P<.0001 [Fisher's 2×2]) when the classes of mutations were dichotomized into frameshift and nonsense (Trunc) versus all other types and when tested against phenotype (PHS vs. GCPS). B, Diagram of the position within the gene of known nonsense, frameshift, and splice-site mutations. Some of the closely spaced mutations have been adjusted for increased visual clarity. Splice-site mutations are shown in red. Black numbers indicate identical mutations, and red numbers indicate multiple mutations in the same splice donor. Data include published mutations (Bianchi et al. 1981; Tommerup and Nielsen 1983; Marks et al. 1985; Pelz et al. 1986; Wagner et al. 1990; Pettigrew et al. 1991; Vortkamp et al. 1991; Kang et al. 1997b; Radhakrishna et al. 1997, 1999; Wild et al. 1997; Williams et al. 1997; Kalff-Suske et al. 1999, 2000a, 2000b, 2004; Friez and Stevenson 2000; Killoran et al. 2000; Galasso et al. 2001; Kroisel et al. 2001; Elson et al. 2002; Debeer et al. 2003; Driess et al. 2003; Freese et al. 2003; Johnston et al. 2003; Kremer et al. 2003; Turner et al. 2003; Ng et al. 2004) and the mutations identified in the present study. The colored bars on the protein show the conserved domains of GLI3 as defined elsewhere (Ruppert et al. 1990). The American Journal of Human Genetics 2005 76, 609-622DOI: (10.1086/429346) Copyright © 2005 The American Society of Human Genetics Terms and Conditions