Search

Your search keyword '"Wilson, Louise C."' showing total 234 results
Start Over Author "Wilson, Louise C."
234 results on '"Wilson, Louise C."'

1. Regulatory elements in SEM1-DLX5-DLX6 (7q21.3) locus contribute to genetic control of coronal nonsyndromic craniosynostosis and bone density-related traits

Author

Nicoletti, Paola, Zafer, Samreen, Matok, Lital, Irron, Inbar, Patrick, Meidva, Haklai, Rotem, Evangelista, John Erol, Marino, Giacomo B., Ma’ayan, Avi, Sewda, Anshuman, Holmes, Greg, Britton, Sierra R., Lee, Won Jun, Wu, Meng, Ru, Ying, Arnaud, Eric, Botto, Lorenzo, Brody, Lawrence C., Byren, Jo C., Caggana, Michele, Carmichael, Suzan L., Cilliers, Deirdre, Conway, Kristin, Crawford, Karen, Cuellar, Araceli, Di Rocco, Federico, Engel, Michael, Fearon, Jeffrey, Feldkamp, Marcia L., Finnell, Richard, Fisher, Sarah, Freudlsperger, Christian, Garcia-Fructuoso, Gemma, Hagge, Rhinda, Heuzé, Yann, Harshbarger, Raymond J., Hobbs, Charlotte, Howley, Meredith, Jenkins, Mary M., Johnson, David, Justice, Cristina M., Kane, Alex, Kay, Denise, Gosain, Arun Kumar, Langlois, Peter, Legal-Mallet, Laurence, Lin, Angela E., Mills, James L., Morton, Jenny E.V., Noons, Peter, Olshan, Andrew, Persing, John, Phipps, Julie M., Redett, Richard, Reefhuis, Jennita, Rizk, Elias, Samson, Thomas D., Shaw, Gary M., Sicko, Robert, Smith, Nataliya, Staffenberg, David, Stoler, Joan, Sweeney, Elizabeth, Taub, Peter J., Timberlake, Andrew T., Topczewska, Jolanta, Wall, Steven A., Wilson, Alexander F., Wilson, Louise C., Boyadjiev, Simeon A., Wilkie, Andrew O.M., Richtsmeier, Joan T., Jabs, Ethylin Wang, Romitti, Paul A., Karasik, David, Birnbaum, Ramon Y., and Peter, Inga

Published
2024
Full Text
View/download PDF

2. Pathogenic variants in the paired-related homeobox 1 gene (PRRX1) cause craniosynostosis with incomplete penetrance

Author

Tooze, Rebecca S., Miller, Kerry A., Swagemakers, Sigrid M.A., Calpena, Eduardo, McGowan, Simon J., Boute, Odile, Collet, Corinne, Johnson, David, Laffargue, Fanny, de Leeuw, Nicole, Morton, Jenny V., Noons, Peter, Ockeloen, Charlotte W., Phipps, Julie M., Tan, Tiong Yang, Timberlake, Andrew T., Vanlerberghe, Clemence, Wall, Steven A., Weber, Astrid, Wilson, Louise C., Zackai, Elaine H., Mathijssen, Irene M.J., Twigg, Stephen R.F., and Wilkie, Andrew O.M.

Published
2023
Full Text
View/download PDF

3. A genome-wide association study implicates the BMP7 locus as a risk factor for nonsyndromic metopic craniosynostosis

Author

Justice, Cristina M, Cuellar, Araceli, Bala, Krithi, Sabourin, Jeremy A, Cunningham, Michael L, Crawford, Karen, Phipps, Julie M, Zhou, Yan, Cilliers, Deirdre, Byren, Jo C, Johnson, David, Wall, Steven A, Morton, Jenny EV, Noons, Peter, Sweeney, Elizabeth, Weber, Astrid, Rees, Katie EM, Wilson, Louise C, Simeonov, Emil, Kaneva, Radka, Yaneva, Nadezhda, Georgiev, Kiril, Bussarsky, Assen, Senders, Craig, Zwienenberg, Marike, Boggan, James, Roscioli, Tony, Tamburrini, Gianpiero, Barba, Marta, Conway, Kristin, Sheffield, Val C, Brody, Lawrence, Mills, James L, Kay, Denise, Sicko, Robert J, Langlois, Peter H, Tittle, Rachel K, Botto, Lorenzo D, Jenkins, Mary M, LaSalle, Janine M, Lattanzi, Wanda, Wilkie, Andrew OM, Wilson, Alexander F, Romitti, Paul A, and Boyadjiev, Simeon A

Subjects
Genetics, Complementary and Alternative Medicine, Paediatrics and Reproductive Medicine, Genetics & Heredity, Reproductive medicine
Abstract

Our previous genome-wide association study (GWAS) for sagittal nonsyndromic craniosynostosis (sNCS) provided important insights into the genetics of midline CS. In this study, we performed a GWAS for a second midline NCS, metopic NCS (mNCS), using 215 non-Hispanic white case-parent triads. We identified six variants with genome-wide significance (P ≤ 5 × 10–8): rs781716 (P = 4.71 × 10–9; odds ratio [OR] = 2.44) intronic to SPRY3; rs6127972 (P = 4.41 × 10–8; OR = 2.17) intronic to BMP7; rs62590971 (P = 6.22 × 10–9; OR = 0.34), located ~ 155 kb upstream from TGIF2LX; and rs2522623, rs2573826, and rs2754857, all intronic to PCDH11X (P = 1.76 × 10–8, OR = 0.45; P = 3.31 × 10–8, OR = 0.45; P = 1.09 × 10–8, OR = 0.44, respectively). We performed a replication study of these variants using an independent non-Hispanic white sample of 194 unrelated mNCS cases and 333 unaffected controls; only the association for rs6127972 (P = 0.004, OR = 1.45; meta-analysis P = 1.27 × 10–8, OR = 1.74) was replicated. Our meta-analysis examining single nucleotide polymorphisms common to both our mNCS and sNCS studies showed the strongest association for rs6127972 (P = 1.16 × 10–6). Our imputation analysis identified a linkage disequilibrium block encompassing rs6127972, which contained an enhancer overlapping a CTCF transcription factor binding site (chr20:55,798,821–55,798,917) that was significantly hypomethylated in mesenchymal stem cells derived from fused metopic compared to open sutures from the same probands. This study provides additional insights into genetic factors in midline CS.

Published
2020

5. A Comparison of Structural Variant Calling from Short-Read and Nanopore-Based Whole-Genome Sequencing Using Optical Genome Mapping as a Benchmark.

Author

Pei, Yang, Tanguy, Melanie, Giess, Adam, Dixit, Abhijit, Wilson, Louise C., Gibbons, Richard J., Twigg, Stephen R. F., Elgar, Greg, and Wilkie, Andrew O. M.

Subjects
WHOLE genome sequencing, GENE mapping, DNA copy number variations, GENOMES, GENOMICS
Abstract

The identification of structural variants (SVs) in genomic data represents an ongoing challenge because of difficulties in reliable SV calling leading to reduced sensitivity and specificity. We prepared high-quality DNA from 9 parent–child trios, who had previously undergone short-read whole-genome sequencing (Illumina platform) as part of the Genomics England 100,000 Genomes Project. We reanalysed the genomes using both Bionano optical genome mapping (OGM; 8 probands and one trio) and Nanopore long-read sequencing (Oxford Nanopore Technologies [ONT] platform; all samples). To establish a "truth" dataset, we asked whether rare proband SV calls (n = 234) made by the Bionano Access (version 1.6.1)/Solve software (version 3.6.1_11162020) could be verified by individual visualisation using the Integrative Genomics Viewer with either or both of the Illumina and ONT raw sequence. Of these, 222 calls were verified, indicating that Bionano OGM calls have high precision (positive predictive value 95%). We then asked what proportion of the 222 true Bionano SVs had been identified by SV callers in the other two datasets. In the Illumina dataset, sensitivity varied according to variant type, being high for deletions (115/134; 86%) but poor for insertions (13/58; 22%). In the ONT dataset, sensitivity was generally poor using the original Sniffles variant caller (48% overall) but improved substantially with use of Sniffles2 (36/40; 90% and 17/23; 74% for deletions and insertions, respectively). In summary, we show that the precision of OGM is very high. In addition, when applying the Sniffles2 caller, the sensitivity of SV calling using ONT long-read sequence data outperforms Illumina sequencing for most SV types. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

8. Loss-of-function HDAC8 mutations cause a phenotypic spectrum of Cornelia de Lange syndrome-like features, ocular hypertelorism, large fontanelle and X-linked inheritance.

Author

Kaiser, Frank J, Ansari, Morad, Braunholz, Diana, Concepción Gil-Rodríguez, María, Decroos, Christophe, Wilde, Jonathan J, Fincher, Christopher T, Kaur, Maninder, Bando, Masashige, Amor, David J, Atwal, Paldeep S, Bahlo, Melanie, Bowman, Christine M, Bradley, Jacquelyn J, Brunner, Han G, Clark, Dinah, Del Campo, Miguel, Di Donato, Nataliya, Diakumis, Peter, Dubbs, Holly, Dyment, David A, Eckhold, Juliane, Ernst, Sarah, Ferreira, Jose C, Francey, Lauren J, Gehlken, Ulrike, Guillén-Navarro, Encarna, Gyftodimou, Yolanda, Hall, Bryan D, Hennekam, Raoul, Hudgins, Louanne, Hullings, Melanie, Hunter, Jennifer M, Yntema, Helger, Innes, A Micheil, Kline, Antonie D, Krumina, Zita, Lee, Hane, Leppig, Kathleen, Lynch, Sally Ann, Mallozzi, Mark B, Mannini, Linda, McKee, Shane, Mehta, Sarju G, Micule, Ieva, Care4Rare Canada Consortium, Mohammed, Shehla, Moran, Ellen, Mortier, Geert R, Moser, Joe-Ann S, Noon, Sarah E, Nozaki, Naohito, Nunes, Luis, Pappas, John G, Penney, Lynette S, Pérez-Aytés, Antonio, Petersen, Michael B, Puisac, Beatriz, Revencu, Nicole, Roeder, Elizabeth, Saitta, Sulagna, Scheuerle, Angela E, Schindeler, Karen L, Siu, Victoria M, Stark, Zornitza, Strom, Samuel P, Thiese, Heidi, Vater, Inga, Willems, Patrick, Williamson, Kathleen, Wilson, Louise C, University of Washington Center for Mendelian Genomics, Hakonarson, Hakon, Quintero-Rivera, Fabiola, Wierzba, Jolanta, Musio, Antonio, Gillessen-Kaesbach, Gabriele, Ramos, Feliciano J, Jackson, Laird G, Shirahige, Katsuhiko, Pié, Juan, Christianson, David W, Krantz, Ian D, Fitzpatrick, David R, and Deardorff, Matthew A

Subjects
Care4Rare Canada Consortium, University of Washington Center for Mendelian Genomics, Humans, Hypertelorism, De Lange Syndrome, Eye Abnormalities, Histone Deacetylases, Repressor Proteins, Cohort Studies, Sequence Alignment, Amino Acid Sequence, Phenotype, Mutation, Missense, Molecular Sequence Data, Child, Child, Preschool, Infant, Female, Male, Genes, X-Linked, Cranial Fontanelles, Genetics, Rare Diseases, Dental/Oral and Craniofacial Disease, Intellectual and Developmental Disabilities (IDD), Pediatric, Brain Disorders, 2.1 Biological and endogenous factors, 4.1 Discovery and preclinical testing of markers and technologies, Detection, screening and diagnosis, Aetiology, Congenital, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

Cornelia de Lange syndrome (CdLS) is a multisystem genetic disorder with distinct facies, growth failure, intellectual disability, distal limb anomalies, gastrointestinal and neurological disease. Mutations in NIPBL, encoding a cohesin regulatory protein, account for >80% of cases with typical facies. Mutations in the core cohesin complex proteins, encoded by the SMC1A, SMC3 and RAD21 genes, together account for ∼5% of subjects, often with atypical CdLS features. Recently, we identified mutations in the X-linked gene HDAC8 as the cause of a small number of CdLS cases. Here, we report a cohort of 38 individuals with an emerging spectrum of features caused by HDAC8 mutations. For several individuals, the diagnosis of CdLS was not considered prior to genomic testing. Most mutations identified are missense and de novo. Many cases are heterozygous females, each with marked skewing of X-inactivation in peripheral blood DNA. We also identified eight hemizygous males who are more severely affected. The craniofacial appearance caused by HDAC8 mutations overlaps that of typical CdLS but often displays delayed anterior fontanelle closure, ocular hypertelorism, hooding of the eyelids, a broader nose and dental anomalies, which may be useful discriminating features. HDAC8 encodes the lysine deacetylase for the cohesin subunit SMC3 and analysis of the functional consequences of the missense mutations indicates that all cause a loss of enzymatic function. These data demonstrate that loss-of-function mutations in HDAC8 cause a range of overlapping human developmental phenotypes, including a phenotypically distinct subgroup of CdLS.

Published
2014

9. Mutations in the Gene Encoding IFT Dynein Complex Component WDR34 Cause Jeune Asphyxiating Thoracic Dystrophy

Author

Schmidts, Miriam, Vodopiutz, Julia, Christou-Savina, Sonia, Cortés, Claudio R, McInerney-Leo, Aideen M, Emes, Richard D, Arts, Heleen H, Tüysüz, Beyhan, D’Silva, Jason, Leo, Paul J, Giles, Tom C, Oud, Machteld M, Harris, Jessica A, Koopmans, Marije, Marshall, Mhairi, Elçioglu, Nursel, Kuechler, Alma, Bockenhauer, Detlef, Moore, Anthony T, Wilson, Louise C, Janecke, Andreas R, Hurles, Matthew E, Emmet, Warren, Gardiner, Brooke, Streubel, Berthold, Dopita, Belinda, Zankl, Andreas, Kayserili, Hülya, Scambler, Peter J, Brown, Matthew A, Beales, Philip L, Wicking, Carol, UK10K, Duncan, Emma L, and Mitchison, Hannah M

Subjects
Rare Diseases, Pediatric, Underpinning research, 1.1 Normal biological development and functioning, Generic health relevance, Animals, Asians, Axoneme, Carrier Proteins, Child, Chlamydomonas, Cilia, Cytoplasmic Dyneins, Cytoskeleton, Ellis-Van Creveld Syndrome, Exome, Exons, Humans, Infant, Infant, Newborn, Intracellular Signaling Peptides and Proteins, Mutation, Protein Conformation, Proteomics, Whites, UK10K, Asian People, White People, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

Bidirectional (anterograde and retrograde) motor-based intraflagellar transport (IFT) governs cargo transport and delivery processes that are essential for primary cilia growth and maintenance and for hedgehog signaling functions. The IFT dynein-2 motor complex that regulates ciliary retrograde protein transport contains a heavy chain dynein ATPase/motor subunit, DYNC2H1, along with other less well functionally defined subunits. Deficiency of IFT proteins, including DYNC2H1, underlies a spectrum of skeletal ciliopathies. Here, by using exome sequencing and a targeted next-generation sequencing panel, we identified a total of 11 mutations in WDR34 in 9 families with the clinical diagnosis of Jeune syndrome (asphyxiating thoracic dystrophy). WDR34 encodes a WD40 repeat-containing protein orthologous to Chlamydomonas FAP133, a dynein intermediate chain associated with the retrograde intraflagellar transport motor. Three-dimensional protein modeling suggests that the identified mutations all affect residues critical for WDR34 protein-protein interactions. We find that WDR34 concentrates around the centrioles and basal bodies in mammalian cells, also showing axonemal staining. WDR34 coimmunoprecipitates with the dynein-1 light chain DYNLL1 in vitro, and mining of proteomics data suggests that WDR34 could represent a previously unrecognized link between the cytoplasmic dynein-1 and IFT dynein-2 motors. Together, these data show that WDR34 is critical for ciliary functions essential to normal development and survival, most probably as a previously unrecognized component of the mammalian dynein-IFT machinery.

Published
2013

11. List of Contributors

Author

Acharya, Ganesh, primary, Aertsen, Michael, additional, Afshar, Yalda, additional, Ananth, Cande V., additional, Ashworth, Michael, additional, Au, Patrick, additional, Bakalis, Spyros, additional, Benoist, Guillaume, additional, Bilancia, Colleen G., additional, Bilardo, Caterina M., additional, Bryant, Louise D., additional, Butler, Colin R., additional, Van Calenbergh, Frank, additional, Caritis, Steve N., additional, Chitty, Lyn S., additional, Collins, Patricia, additional, Cook, James, additional, Cuckle, Howard, additional, David, Anna L., additional, De Catte, Luc, additional, De Coppi, Paolo, additional, de Jong-Pleij, Elisabeth, additional, De Keersmaecker, Bart, additional, Deprest, Jan, additional, Devlieger, Roland, additional, de Wert, Guido M., additional, Dickinson, Jan E., additional, Dilworth, Mark, additional, Dondorp, Wybo J., additional, Dunk, Caroline E., additional, Everett, Thomas R., additional, Fisher, Jane, additional, Galan, Henry L., additional, Ganapathi, Mythily, additional, Gardiner, Helena M., additional, Gotherstrom, Cecilia, additional, Harding, Richard, additional, Hewison, Jenny, additional, Hewitt, Richard J., additional, Hiersch, Liran, additional, Hill, Melissa, additional, Hillman, Sara L., additional, Hindryckx, An, additional, Hooper, Stuart B., additional, Huppertz, Berthold, additional, Hutchinson, J. Ciaran, additional, Hyett, Jon, additional, Joyeux, Luc, additional, Jurkovic, Davor, additional, Kingdom, John C., additional, Langlois, Sylvie, additional, Lemon, Lara S., additional, Leruez-Ville, Marianne, additional, Lewi, Liesbeth, additional, Levy, Brynn, additional, Loke, Y.W., additional, Lopriore, Enrico, additional, Macones, George A., additional, Malone, Fergal D., additional, Martirosian, Anahit, additional, McAuliffe, Fionnuala, additional, McDougall, Annie R.A., additional, Moise, Kenneth J., additional, Moffett, Ashley, additional, Müllers, Sieglinde M., additional, Neiger, Ran, additional, Newnham, John P., additional, Obican, Sarah G., additional, Odibo, Anthony O., additional, Oepkes, Dick, additional, Pandya, Pranav P., additional, Platt, Lawrence D., additional, Pratt, Rosalind, additional, Rajah, Kuhan, additional, Rao, Rashmi, additional, Richter, Jute, additional, Rosenbloom, Joshua I., additional, Russo, Francesca Maria, additional, Scialli, Anthony R., additional, Sebire, Neil J., additional, Sharkey, Andrew, additional, Shelmerdine, Susan C., additional, Sibley, Colin, additional, Snowise, Saul, additional, Steggerda, Sylke, additional, Su, Emily J., additional, Tang, Mary, additional, Te Pas, Arjan B., additional, Tita, Alan T., additional, Ushakov, Fred, additional, Van den Veyver, Ignatia B., additional, van Klink, Jeanine M., additional, Venkataramanan, Raman, additional, Ville, Yves, additional, Walkiewicz, Magdalena, additional, Wallis, Colin, additional, Walther-Jallow, Lilian, additional, Wapner, Ronald J., additional, Westgren, Magnus, additional, White, Scott W., additional, Wilson, Louise C., additional, Wilson, R. Douglas, additional, Winkelhorst, Dian, additional, Winyard, Paul J.D., additional, Wohlmuth, Christoph, additional, Wou, Karen, additional, Yaron, Yuval, additional, Leung, Kwok Yin, additional, and Yulia, Angela, additional

Published
2020
Full Text
View/download PDF

12. The ARID1B spectrum in 143 patients: from nonsyndromic intellectual disability to Coffin–Siris syndrome

Author

van der Sluijs, Pleuntje J., Jansen, Sandra, Vergano, Samantha A., Adachi-Fukuda, Miho, Alanay, Yasemin, AlKindy, Adila, Baban, Anwar, Bayat, Allan, Beck-Wödl, Stefanie, Berry, Katherine, Bijlsma, Emilia K., Bok, Levinus A., Brouwer, Alwin F. J., van der Burgt, Ineke, Campeau, Philippe M., Canham, Natalie, Chrzanowska, Krystyna, Chu, Yoyo W. Y., Chung, Brain H. Y., Dahan, Karin, De Rademaeker, Marjan, Destree, Anne, Dudding-Byth, Tracy, Earl, Rachel, Elcioglu, Nursel, Elias, Ellen R., Fagerberg, Christina, Gardham, Alice, Gener, Blanca, Gerkes, Erica H., Grasshoff, Ute, van Haeringen, Arie, Heitink, Karin R., Herkert, Johanna C., den Hollander, Nicolette S., Horn, Denise, Hunt, David, Kant, Sarina G., Kato, Mitsuhiro, Kayserili, Hülya, Kersseboom, Rogier, Kilic, Esra, Krajewska-Walasek, Malgorzata, Lammers, Kylin, Laulund, Lone W., Lederer, Damien, Lees, Melissa, López-González, Vanesa, Maas, Saskia, Mancini, Grazia M. S., Marcelis, Carlo, Martinez, Francisco, Maystadt, Isabelle, McGuire, Marianne, McKee, Shane, Mehta, Sarju, Metcalfe, Kay, Milunsky, Jeff, Mizuno, Seiji, Moeschler, John B., Netzer, Christian, Ockeloen, Charlotte W., Oehl-Jaschkowitz, Barbara, Okamoto, Nobuhiko, Olminkhof, Sharon N. M., Orellana, Carmen, Pasquier, Laurent, Pottinger, Caroline, Riehmer, Vera, Robertson, Stephen P., Roifman, Maian, Rooryck, Caroline, Ropers, Fabienne G., Rosello, Monica, Ruivenkamp, Claudia A. L., Sagiroglu, Mahmut S., Sallevelt, Suzanne C. E. H., Sanchis Calvo, Amparo, Simsek-Kiper, Pelin O., Soares, Gabriela, Solaeche, Lucia, Sonmez, Fatma Mujgan, Splitt, Miranda, Steenbeek, Duco, Stegmann, Alexander P. A., Stumpel, Constance T. R. M., Tanabe, Saori, Uctepe, Eyyup, Utine, G. Eda, Veenstra-Knol, Hermine E., Venkateswaran, Sunita, Vilain, Catheline, Vincent-Delorme, Catherine, Vulto-van Silfhout, Anneke T., Wheeler, Patricia, Wilson, Golder N., Wilson, Louise C., Wollnik, Bernd, Kosho, Tomoki, Wieczorek, Dagmar, Eichler, Evan, Pfundt, Rolph, de Vries, Bert B. A., Clayton-Smith, Jill, and Santen, Gijs W. E.

Published
2019
Full Text
View/download PDF

13. Identification of 34 novel and 56 known FOXL2 mutations in patients with blepharophimosis syndrome

Author

Beysen, Diane, De Jaegere, Sarah, Amor, David, Bouchard, Philippe, Christin‐Maitre, Sophie, Fellous, Marc, Touraine, Philippe, Grix, Arthur W, Hennekam, Raoul, Meire, Françoise, Oyen, Nina, Wilson, Louise C, Barel, Dalit, Clayton‐Smith, Jill, de Ravel, Thomy, Decock, Christian, Delbeke, Patricia, Ensenauer, Regina, Ebinger, Friedrich, Gillessen‐Kaesbach, Gabriele, Hendriks, Yvonne, Kimonis, Virginia, Laframboise, Rachel, Laissue, Paul, Leppig, Kathleen, Leroy, Bart P, Miller, David T, Mowat, David, Neumann, Luitgard, Plomp, Astrid, Van Regemorter, Nicole, Wieczorek, Dagmar, Veitia, Reiner A, De Paepe, Anne, and De Baere, Elfride

Subjects
Genetics, Rare Diseases, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Adolescent, Adult, Amino Acid Sequence, Blepharophimosis, Child, Child, Preschool, Codon, Nonsense, DNA Mutational Analysis, Eyelids, Female, Forkhead Box Protein L2, Forkhead Transcription Factors, Frameshift Mutation, Genotype, Humans, Infant, Infant, Newborn, Male, Middle Aged, Molecular Sequence Data, Mutation, Missense, Pedigree, Phenotype, Primary Ovarian Insufficiency, Sequence Alignment, Young Adult, Clinical Sciences, Genetics & Heredity
Abstract

Blepharophimosis syndrome (BPES) is caused by loss-of-function mutations in the single-exon forkhead transcription factor gene FOXL2 and by genomic rearrangements of the FOXL2 locus. Here, we focus on 92 new intragenic FOXL2 mutations, 34 of which are novel. Specifically, we found 10 nonsense mutations (11%), 13 missense mutations (14%), 40 deletions or insertions leading to a frameshift (43%), and 29 in-frame changes (32%), of which 28 (30%) lead to a polyalanine expansion. This study confirms the existence of two previously described mutational hotspots. Moreover, we gained novel insights in genotype-phenotype correlations, emphasizing the need to interpret genotype-phenotype correlations individually and always in the context of further clinical observations.

Published
2008

16. Whole genome sequencing of ‘mutation-negative’ individuals with Cornelia de Lange Syndrome

Author

Ansari, Morad, primary, Halachev, Mihail, additional, Parry, David, additional, Campos, Jose L., additional, D’Souza, Elston N., additional, Barnett, Christopher, additional, Wilkie, Andrew O. M., additional, Barnicoat, Angela, additional, Patel, Chirag V., additional, Sukarova-Angelovska, Elena, additional, Girisha, Katta M., additional, Firth, Helen V., additional, Prescott, Katrina, additional, Wilson, Louise C., additional, McEntagart, Meriel, additional, Davidson, Rosemarie, additional, Lynch, Sally Ann, additional, Joss, Shelagh, additional, Holden, Simon T., additional, Lam, Wayne K., additional, Sisodiya, Sanjay M., additional, Green, Andrew J., additional, Poke, Gemma, additional, Whiffin, Nicola, additional, FitzPatrick, David R., additional, and Meynert, Alison, additional

Published
2022
Full Text
View/download PDF

17. Correction: The ARID1B spectrum in 143 patients: from nonsyndromic intellectual disability to Coffin–Siris syndrome

Author

van der Sluijs, Pleuntje J., Jansen, Sandra, Vergano, Samantha A., Adachi-Fukuda, Miho, Alanay, Yasemin, AlKindy, Adila, Baban, Anwar, Bayat, Allan, Beck-Wödl, Stefanie, Berry, Katherine, Bijlsma, Emilia K., Bok, Levinus A., Brouwer, Alwin F. J., van der Burgt, Ineke, Campeau, Philippe M., Canham, Natalie, Chrzanowska, Krystyna, Chu, Yoyo W. Y., Chung, Brain H. Y., Dahan, Karin, De Rademaeker, Marjan, Destree, Anne, Dudding-Byth, Tracy, Earl, Rachel, Elcioglu, Nursel, Elias, Ellen R., Fagerberg, Christina, Gardham, Alice, Gener, Blanca, Gerkes, Erica H., Grasshoff, Ute, van Haeringen, Arie, Heitink, Karin R., Herkert, Johanna C., den Hollander, Nicolette S., Horn, Denise, Hunt, David, Kant, Sarina G., Kato, Mitsuhiro, Kayserili, Hülya, Kersseboom, Rogier, Kilic, Esra, Krajewska-Walasek, Malgorzata, Lammers, Kylin, Laulund, Lone W., Lederer, Damien, Lees, Melissa, López-González, Vanesa, Maas, Saskia, Mancini, Grazia M. S., Marcelis, Carlo, Martinez, Francisco, Maystadt, Isabelle, McGuire, Marianne, McKee, Shane, Mehta, Sarju, Metcalfe, Kay, Milunsky, Jeff, Mizuno, Seiji, Moeschler, John B., Netzer, Christian, Ockeloen, Charlotte W., Oehl-Jaschkowitz, Barbara, Okamoto, Nobuhiko, Olminkhof, Sharon N. M., Orellana, Carmen, Pasquier, Laurent, Pottinger, Caroline, Riehmer, Vera, Robertson, Stephen P., Roifman, Maian, Rooryck, Caroline, Ropers, Fabienne G., Rosello, Monica, Ruivenkamp, Claudia A. L., Sagiroglu, Mahmut S., Sallevelt, Suzanne C. E. H., Calvo, Amparo Sanchis, Simsek-Kiper, Pelin O., Soares, Gabriela, Solaeche, Lucia, Sonmez, Fatma Mujgan, Splitt, Miranda, Steenbeek, Duco, Stegmann, Alexander P. A., Stumpel, Constance T. R. M., Tanabe, Saori, Uctepe, Eyyup, Utine, G. Eda, Veenstra-Knol, Hermine E., Venkateswaran, Sunita, Vilain, Catheline, Vincent-Delorme, Catherine, Vulto-van Silfhout, Anneke T., Wheeler, Patricia, Wilson, Golder N., Wilson, Louise C., Wollnik, Bernd, Kosho, Tomoki, Wieczorek, Dagmar, Eichler, Evan, Pfundt, Rolph, de Vries, Bert B. A., Clayton-Smith, Jill, and Santen, Gijs W. E.

Published
2019
Full Text
View/download PDF

18. Evaluating the performance of a clinical genome sequencing program for diagnosis of rare genetic disease, seen through the lens of craniosynostosis

Author

Hyder, Zerin, primary, Calpena, Eduardo, additional, Pei, Yang, additional, Tooze, Rebecca S., additional, Brittain, Helen, additional, Twigg, Stephen R.F., additional, Cilliers, Deirdre, additional, Morton, Jenny E.V., additional, McCann, Emma, additional, Weber, Astrid, additional, Wilson, Louise C., additional, Douglas, Andrew G.L., additional, McGowan, Ruth, additional, Need, Anna, additional, Bond, Andrew, additional, Tavares, Ana Lisa Taylor, additional, Thomas, Ellen R.A., additional, Ambrose, John C., additional, Arumugam, Prabhu, additional, Bevers, Roel, additional, Bleda, Marta, additional, Boustred, Christopher R., additional, Chan, Georgia C., additional, Elgar, Greg, additional, Fowler, Tom, additional, Giess, Adam, additional, Hamblin, Angela, additional, Henderson, Shirley, additional, Hubbard, Tim J.P., additional, Jackson, Rob, additional, Jones, Louise J., additional, Kasperaviciute, Dalia, additional, Kayikci, Melis, additional, Kousathanas, Athanasios, additional, Lahnstein, Lea, additional, Leigh, Sarah E.A., additional, Leong, Ivonne U.S., additional, Lopez, Javier F., additional, Maleady-Crowe, Fiona, additional, McEntagart, Meriel, additional, Minneci, Federico, additional, Moutsianas, Loukas, additional, Mueller, Michael, additional, Murugaesu, Nirupa, additional, O’Donovan, Peter, additional, Odhams, Chris A., additional, Patch, Christine, additional, Pereira, Mariana Buongermino, additional, Perez-Gil, Daniel, additional, Pullinger, John, additional, Rahim, Tahrima, additional, Rendon, Augusto, additional, Rogers, Tim, additional, Savage, Kevin, additional, Sawant, Kushmita, additional, Siddiq, Afshan, additional, Sieghart, Alexander, additional, Smith, Samuel C., additional, Sosinsky, Alona, additional, Stuckey, Alexander, additional, Tanguy, Mélanie, additional, Thompson, Simon R., additional, Tucci, Arianna, additional, Welland, Matthew J., additional, Williams, Eleanor, additional, Witkowska, Katarzyna, additional, Wood, Suzanne M., additional, Hill, Susan L., additional, Deans, Zandra C., additional, Boardman-Pretty, Freya, additional, Caulfield, Mark, additional, Scott, Richard H., additional, and Wilkie, Andrew O.M., additional

Published
2021
Full Text
View/download PDF

19. Obesity-Associated GNAS Mutations and the Melanocortin Pathway

Author

Mendes de Oliveira, Edson, primary, Keogh, Julia M., additional, Talbot, Fleur, additional, Henning, Elana, additional, Ahmed, Rachel, additional, Perdikari, Aliki, additional, Bounds, Rebecca, additional, Wasiluk, Natalia, additional, Ayinampudi, Vikram, additional, Barroso, Inês, additional, Mokrosiński, Jacek, additional, Jyothish, Deepthi, additional, Lim, Sharon, additional, Gupta, Sanjay, additional, Kershaw, Melanie, additional, Matei, Cristina, additional, Partha, Praveen, additional, Randell, Tabitha, additional, McAulay, Antoinette, additional, Wilson, Louise C., additional, Cheetham, Tim, additional, Crowne, Elizabeth C., additional, Clayton, Peter, additional, and Farooqi, I. Sadaf, additional

Published
2021
Full Text
View/download PDF

22. A Study of the Clinical and Radiological Features in a Cohort of 93 Patients with a COL2A1 Mutation Causing Spondyloepiphyseal Dysplasia Congenita or a Related Phenotype

Author

Terhal, Paulien A., Nievelstein, Rutger Jan A. J., Verver, Eva J. J., Topsakal, Vedat, van Dommelen, Paula, Hoornaert, Kristien, Le Merrer, Martine, Zankl, Andreas, Simon, Marleen E. H., Smithson, Sarah F., Marcelis, Carlo, Kerr, Bronwyn, Clayton-Smith, Jill, Kinning, Esther, Mansour, Sahar, Elmslie, Frances, Goodwin, Linda, van der Hout, Annemarie H., Veenstra-Knol, Hermine E., Herkert, Johanna C., Lund, Allan M., Hennekam, Raoul C. M., Mégarbané, André, Lees, Melissa M., Wilson, Louise C., Male, Alison, Hurst, Jane, Alanay, Yasemin, Annerén, Göran, Betz, Regina C., Bongers, Ernie M. H. F., Cormier-Daire, Valerie, Dieux, Anne, David, Albert, Elting, Mariet W., van den Ende, Jenneke, Green, Andrew, van Hagen, Johanna M., Hertel, Niels Thomas, Holder-Espinasse, Muriel, den Hollander, Nicolette, Homfray, Tessa, Hove, Hanne D., Price, Susan, Raas-Rothschild, Annick, Rohrbach, Marianne, Schroeter, Barbara, Suri, Mohnish, Thompson, Elizabeth M., Tobias, Edward S., Toutain, Annick, Vreeburg, Maaike, Wakeling, Emma, Knoers, Nine V., Coucke, Paul, and Mortier, Geert R.

Published
2015
Full Text
View/download PDF

24. SMAD6 variants in craniosynostosis: genotype and phenotype evaluation

Author

Calpena, Eduardo, Cuellar, Araceli, Bala, Krithi, Swagemakers, Sigrid M. A., Koelling, Nil, Mcgowan, Simon J., Phipps, Julie M., Balasubramanian, Meena, Cunningham, Michael L., Douzgou, Sofia, Lattanzi, Wanda, Morton, Jenny E. V., Shears, Deborah, Weber, Astrid, Wilson, Louise C., Lord, Helen, Lester, Tracy, Johnson, David, Wall, Steven A., Twigg, Stephen R. F., Mathijssen, Irene M. J., England Research Consortium, Genomic, Boyadjiev, Simeon A., Wilkie, Andrew O. M., Wanda Lattanzi (ORCID:0000-0003-3092-4936), Calpena, Eduardo, Cuellar, Araceli, Bala, Krithi, Swagemakers, Sigrid M. A., Koelling, Nil, Mcgowan, Simon J., Phipps, Julie M., Balasubramanian, Meena, Cunningham, Michael L., Douzgou, Sofia, Lattanzi, Wanda, Morton, Jenny E. V., Shears, Deborah, Weber, Astrid, Wilson, Louise C., Lord, Helen, Lester, Tracy, Johnson, David, Wall, Steven A., Twigg, Stephen R. F., Mathijssen, Irene M. J., England Research Consortium, Genomic, Boyadjiev, Simeon A., Wilkie, Andrew O. M., and Wanda Lattanzi (ORCID:0000-0003-3092-4936)

Abstract

Purpose: Enrichment of heterozygous missense and truncating SMAD6 variants was previously reported in non-syndromic sagittal and metopic synostosis, and interaction of SMAD6 variants with a common polymorphism near BMP2 (rs1884302) was proposed to contribute to inconsistent penetrance. We determined the occurrence of SMAD6 variants in all types of craniosynostosis, evaluated the impact of different missense variants on SMAD6 function, and tested independently whether rs1884302 genotype significantly modifies the phenotype. Methods: We performed resequencing of SMAD6 in 795 unsolved patients with any type of craniosynostosis and genotyped rs1884302 in SMAD6-positive individuals and relatives. We examined the inhibitory activity and stability of SMAD6 missense variants. Results: We found 18 (2.3%) different rare damaging SMAD6 variants, with the highest prevalence in metopic synostosis (5.8%) and an 18.3-fold enrichment of loss-of-function variants compared to gnomAD data (P<10-7). Combined with eight additional variants, ≥20/26 were transmitted from an unaffected parent but rs1884302 genotype did not predict phenotype. Conclusion: Pathogenic SMAD6 variants substantially increase the risk of both nonsyndromic and syndromic presentations of craniosynostosis, especially metopic synostosis. Functional analysis is important to evaluate missense variants. Genotyping of rs1884302 is not clinically useful. Mechanisms to explain the remarkable diversity of phenotypes associated with SMAD6 variants remain obscure.

Published
2020

26. The origin of EFNB1 mutations in craniofrontonasal syndrome: Frequent somatic mosaicism and explanation of the paucity of carrier males

Author

Twigg, Stephen R.F., Matsumoto, Kazuya, Kidd, Alexa M.J., Goriely, Anne, Taylor, Indira B., Fisher, Richard B., Hoogeboom, A., Jeannette M., Mathijssen, Irene M.J., Lourenco, M. Teresa, Morton, Jenny E.V., Sweeney, Elizabeth, Wilson, Louise C., Brunner, Han G., Mulliken, John B., Wall, Steven A., and Wilkie, Andrew O.M.

Subjects
Gene mutations -- Research, Mosaicism -- Health aspects, Biological sciences
Abstract

The discovery of causative mutations in the EFNB1 gene is exploited, which encodes ephrin-B1, to survey the molecular alterations in 59 families. Somatic mosaicism was demonstrated in 6 of 53 informative families, and of 17 germline mutations in individuals for whom the parental origin of mutation could be demonstrated, 15 arose from the father.

Published
2006

34. Correction: SMAD6 variants in craniosynostosis: genotype and phenotype evaluation

Author

Calpena, Eduardo, primary, Cuellar, Araceli, additional, Bala, Krithi, additional, Swagemakers, Sigrid M.A., additional, Koelling, Nils, additional, McGowan, Simon J., additional, Phipps, Julie M., additional, Balasubramanian, Meena, additional, Cunningham, Michael L., additional, Douzgou, Sofia, additional, Lattanzi, Wanda, additional, Morton, Jenny E.V., additional, Shears, Deborah, additional, Weber, Astrid, additional, Wilson, Louise C., additional, Lord, Helen, additional, Lester, Tracy, additional, Johnson, David, additional, Wall, Steven A., additional, Twigg, Stephen R.F., additional, Mathijssen, Irene M.J., additional, Boardman-Pretty, Freya, additional, Boyadjiev, Simeon A., additional, and Wilkie, Andrew O.M., additional

Published
2020
Full Text
View/download PDF

35. SMAD6 variants in craniosynostosis: genotype and phenotype evaluation

Author

Calpena, Eduardo, primary, Cuellar, Araceli, additional, Bala, Krithi, additional, Swagemakers, Sigrid M.A., additional, Koelling, Nils, additional, McGowan, Simon J., additional, Phipps, Julie M., additional, Balasubramanian, Meena, additional, Cunningham, Michael L., additional, Douzgou, Sofia, additional, Lattanzi, Wanda, additional, Morton, Jenny E.V., additional, Shears, Deborah, additional, Weber, Astrid, additional, Wilson, Louise C., additional, Lord, Helen, additional, Lester, Tracy, additional, Johnson, David, additional, Wall, Steven A., additional, Twigg, Stephen R.F., additional, Mathijssen, Irene M.J., additional, Boardman-Pretty, Freya, additional, Boyadjiev, Simeon A., additional, and Wilkie, Andrew O.M., additional

Published
2020
Full Text
View/download PDF

37. Molecular and clinical characterization of cardio-facio-cutaneous (CFC) syndrome: Overlapping clinical manifestations with Costello syndrome

Author

Narumi, Yoko, Aoki, Yoko, Niihori, Tetsuya, Neri, Giovanni, Cavé, Hélène, Verloes, Alain, Nava, Caroline, Kavamura, Maria Ines, Okamoto, Nobuhiko, Kurosawa, Kenji, Hennekam, Raoul C.M., Wilson, Louise C., Gillessen-Kaesbach, Gabriele, Wieczorek, Dagmar, Lapunzina, Pablo, Ohashi, Hirofumi, Makita, Yoshio, Kondo, Ikuko, Tsuchiya, Shigeru, Ito, Etsuro, Sameshima, Kiyoko, Kato, Kumi, Kure, Shigeo, and Matsubara, Yoichi

Published
2007
Full Text
View/download PDF

40. The ARID1B spectrum in 143 patients: from nonsyndromic intellectual disability to Coffin–Siris syndrome

Author

Karabey, Hülya Kayserili (ORCID 0000-0003-0376-499X & YÖK ID 7945), van der Sluijs, Pleuntje J.; Jansen, Sandra; Vergano, Samantha A.; Adachi-Fukuda, Miho; Alanay, Yasemin; AlKindy, Adila; Baban, Anwar; Bayat, Allan; Beck-Woedl, Stefanie; Berry, Katherine; Bijlsma, Emilia K.; Bok, Levinus A.; Brouwer, Alwin F. J.; van der Burgt, Ineke; Campeau, Philippe M.; Canham, Natalie; Chrzanowska, Krystyna; Chu, Yoyo W. Y.; Chung, Brain H. Y.; Dahan, Karin; De Rademaeker, Marjan; Destree, Anne; Dudding-Byth, Tracy; Earl, Rachel; Elçioğlu, Nursel; Elias, Ellen R.; Fagerberg, Christina; Gardham, Alice; Gener, Blanca; Gerkes, Erica H.; Grasshoff, Ute; van Haeringen, Arie; Heitink, Karin R.; Herkert, Johanna C.; den Hollander, Nicolette S.; Horn, Denise; Hunt, David; Kant, Sarina G.; Kato, Mitsuhiro; Kersseboom, Rogier; Kılıç, Esra; Krajewska-Walasek, Malgorzata; Lammers, Kylin; Laulund, Lone W.; Lederer, Damien; Lees, Melissa; Lopez-Gonzalez, Vanesa; Maas, Saskia; Mancini, Grazia M. S.; Marcelis, Carlo; Martinez, Francisco; Maystadt, Isabelle; McGuire, Marianne; McKee, Shane; Mehta, Sarju; Metcalfe, Kay; Milunsky, Jeff; Mizuno, Seiji; Moeschler, John B.; Netzer, Christian; Ockeloen, Charlotte W.; Oehl-Jaschkowitz, Barbara; Okamoto, Nobuhiko; Olminkhof, Sharon N. M.; Orellana, Carmen; Pasquier, Laurent; Pottinger, Caroline; Riehmer, Vera; Robertson, Stephen P.; Roifman, Maian; Rooryck, Caroline; Ropers, Fabienne G.; Rosello, Monica; Ruivenkamp, Claudia A. L.; Sağıroğlu, Mahmut S.; Sallevelt, Suzanne C. E. H.; Sanchis Calvo, Amparo; Şimşek-Kiper, Pelin O.; Soares, Gabriela; Solaeche, Lucia; Sönmez, Fatma Müjgan; Splitt, Miranda; Steenbeek, Duco; Stegmann, Alexander P. A.; Stumpel, Constance T. R. M.; Tanabe, Saori; Üçtepe, Eyyüp; Utine, G. Eda; Veenstra-Knol, Hermine E.; Venkateswaran, Sunita; Vilain, Catheline; Vincent-Delorme, Catherine; Vulto-van Silfhout, Anneke T.; Wheeler, Patricia; Wilson, Golder N.; Wilson, Louise C.; Wollnik, Bernd; Kosho, Tomoki; Wieczorek, Dagmar; Eichler, Evan; Pfundt, Rolph; de Vries, Bert B. A.; Clayton-Smith, Jill; S, School of Medicine, Department of Medical Genetics, Karabey, Hülya Kayserili (ORCID 0000-0003-0376-499X & YÖK ID 7945), van der Sluijs, Pleuntje J.; Jansen, Sandra; Vergano, Samantha A.; Adachi-Fukuda, Miho; Alanay, Yasemin; AlKindy, Adila; Baban, Anwar; Bayat, Allan; Beck-Woedl, Stefanie; Berry, Katherine; Bijlsma, Emilia K.; Bok, Levinus A.; Brouwer, Alwin F. J.; van der Burgt, Ineke; Campeau, Philippe M.; Canham, Natalie; Chrzanowska, Krystyna; Chu, Yoyo W. Y.; Chung, Brain H. Y.; Dahan, Karin; De Rademaeker, Marjan; Destree, Anne; Dudding-Byth, Tracy; Earl, Rachel; Elçioğlu, Nursel; Elias, Ellen R.; Fagerberg, Christina; Gardham, Alice; Gener, Blanca; Gerkes, Erica H.; Grasshoff, Ute; van Haeringen, Arie; Heitink, Karin R.; Herkert, Johanna C.; den Hollander, Nicolette S.; Horn, Denise; Hunt, David; Kant, Sarina G.; Kato, Mitsuhiro; Kersseboom, Rogier; Kılıç, Esra; Krajewska-Walasek, Malgorzata; Lammers, Kylin; Laulund, Lone W.; Lederer, Damien; Lees, Melissa; Lopez-Gonzalez, Vanesa; Maas, Saskia; Mancini, Grazia M. S.; Marcelis, Carlo; Martinez, Francisco; Maystadt, Isabelle; McGuire, Marianne; McKee, Shane; Mehta, Sarju; Metcalfe, Kay; Milunsky, Jeff; Mizuno, Seiji; Moeschler, John B.; Netzer, Christian; Ockeloen, Charlotte W.; Oehl-Jaschkowitz, Barbara; Okamoto, Nobuhiko; Olminkhof, Sharon N. M.; Orellana, Carmen; Pasquier, Laurent; Pottinger, Caroline; Riehmer, Vera; Robertson, Stephen P.; Roifman, Maian; Rooryck, Caroline; Ropers, Fabienne G.; Rosello, Monica; Ruivenkamp, Claudia A. L.; Sağıroğlu, Mahmut S.; Sallevelt, Suzanne C. E. H.; Sanchis Calvo, Amparo; Şimşek-Kiper, Pelin O.; Soares, Gabriela; Solaeche, Lucia; Sönmez, Fatma Müjgan; Splitt, Miranda; Steenbeek, Duco; Stegmann, Alexander P. A.; Stumpel, Constance T. R. M.; Tanabe, Saori; Üçtepe, Eyyüp; Utine, G. Eda; Veenstra-Knol, Hermine E.; Venkateswaran, Sunita; Vilain, Catheline; Vincent-Delorme, Catherine; Vulto-van Silfhout, Anneke T.; Wheeler, Patricia; Wilson, Golder N.; Wilson, Louise C.; Wollnik, Bernd; Kosho, Tomoki; Wieczorek, Dagmar; Eichler, Evan; Pfundt, Rolph; de Vries, Bert B. A.; Clayton-Smith, Jill; S, School of Medicine, and Department of Medical Genetics

Abstract

Purpose: pathogenic variants in ARID1B are one of the most frequent causes of intellectual disability (ID) as determined by large-scale exome sequencing studies. Most studies published thus far describe clinically diagnosed Coffin–Siris patients (ARID1B-CSS) and it is unclear whether these data are representative for patients identified through sequencing of unbiased ID cohorts (ARID1B-ID). We therefore sought to determine genotypic and phenotypic differences between ARID1B-ID and ARID1B-CSS. In parallel, we investigated the effect of different methods of phenotype reporting. Methods: clinicians entered clinical data in an extensive web-based survey. Results: 79 ARID1B-CSS and 64 ARID1B-ID patients were included. CSS-associated dysmorphic features, such as thick eyebrows, long eyelashes, thick alae nasi, long and/or broad philtrum, small nails and small or absent fifth distal phalanx and hypertrichosis, were observed significantly more often (p < 0.001) in ARID1B-CSS patients. No other significant differences were identified. Conclusion: there are only minor differences between ARID1B-ID and ARID1B-CSS patients. ARID1B-related disorders seem to consist of a spectrum, and patients should be managed similarly. We demonstrated that data collection methods without an explicit option to report the absence of a feature (such as most Human Phenotype Ontology-based methods) tended to underestimate gene-related features., Netherlands Organisation for Health Research and Development

Published
2019

43. ERF-related craniosynostosis: The phenotypic and developmental profile of a new craniosynostosis syndrome

Author

Glass, Graeme E., primary, O'Hara, Justine, additional, Canham, Natalie, additional, Cilliers, Deirdre, additional, Dunaway, David, additional, Fenwick, Aimee L., additional, Jeelani, Noor-Owase, additional, Johnson, David, additional, Lester, Tracy, additional, Lord, Helen, additional, Morton, Jenny E. V., additional, Nishikawa, Hiroshi, additional, Noons, Peter, additional, Schwiebert, Kemmy, additional, Shipster, Caroleen, additional, Taylor-Beadling, Alison, additional, Twigg, Stephen R. F., additional, Vasudevan, Pradeep, additional, Wall, Steven A., additional, Wilkie, Andrew O. M., additional, and Wilson, Louise C., additional

Published
2019
Full Text
View/download PDF

44. Biallelic P4HTMvariants associated with HIDEA syndrome and mitochondrial respiratory chain complex I deficiency

Author

Hay, Eleanor, Wilson, Louise C., Hoskins, Bethan, Samuels, Martin, Munot, Pinki, and Rahman, Shamima

Abstract

We report a patient with profound congenital hypotonia, central hypoventilation, poor visual behaviour with retinal hypopigmentation, and significantly decreased mitochondrial respiratory chain complex I activity in muscle, who died at 7 months of age having made minimal developmental progress. Biallelic predicted truncating P4HTMvariants were identified following trio whole-genome sequencing, consistent with a diagnosis of hypotonia, hypoventilation, intellectual disability, dysautonomia, epilepsy and eye abnormalities (HIDEA) syndrome. Very few patients with HIDEA syndrome have been reported previously and mitochondrial abnormalities were observed in three of four previous cases who had a muscle biopsy, suggesting the possibility that HIDEA syndrome represents a primary mitochondrial disorder. P4HTMencodes a transmembrane prolyl 4-hydroxylase with putative targets including hypoxia inducible factors, RNA polymerase II and activating transcription factor 4, which has been implicated in the integrated stress response observed in cell and animal models of mitochondrial disease, and may explain the mitochondrial dysfunction observed in HIDEA syndrome.

Published
2021
Full Text
View/download PDF

45. A New Multisystem Disorder Caused by the Gαs Mutation p.F376V

Author

Biebermann, Heike, primary, Kleinau, Gunnar, additional, Schnabel, Dirk, additional, Bockenhauer, Detlef, additional, Wilson, Louise C, additional, Tully, Ian, additional, Kiff, Sarah, additional, Scheerer, Patrick, additional, Reyes, Monica, additional, Paisdzior, Sarah, additional, Gregory, John W, additional, Allgrove, Jeremy, additional, Krude, Heiko, additional, Mannstadt, Michael, additional, Gardella, Thomas J, additional, Dattani, Mehul, additional, Jüppner, Harald, additional, and Grüters, Annette, additional

Published
2018
Full Text
View/download PDF

46. Cover Image, Volume 176A, Number 4, April 2018

Author

Zarate, Yuri A., primary, Smith-Hicks, Constance L., additional, Greene, Carol, additional, Abbott, Mary-Alice, additional, Siu, Victoria M., additional, Calhoun, Amy R. U. L., additional, Pandya, Arti, additional, Li, Chumei, additional, Sellars, Elizabeth A., additional, Kaylor, Julie, additional, Bosanko, Katherine, additional, Kalsner, Louisa, additional, Basinger, Alice, additional, Slavotinek, Anne M., additional, Perry, Hazel, additional, Saenz, Margarita, additional, Szybowska, Marta, additional, Wilson, Louise C., additional, Kumar, Ajith, additional, Brain, Caroline, additional, Balasubramanian, Meena, additional, Dubbs, Holly, additional, Ortiz-Gonzalez, Xilma R., additional, Zackai, Elaine, additional, Stein, Quinn, additional, Powell, Cynthia M., additional, Schrier Vergano, Samantha, additional, Britt, Allison, additional, Sun, Angela, additional, Smith, Wendy, additional, Bebin, E. Martina, additional, Picker, Jonathan, additional, Kirby, Amelia, additional, Pinz, Hailey, additional, Bombei, Hannah, additional, Mahida, Sonal, additional, Cohen, Julie S., additional, Fatemi, Ali, additional, Vernon, Hilary J., additional, McClellan, Rebecca, additional, Fleming, Leah R., additional, Knyszek, Brittney, additional, Steinraths, Michelle, additional, Velasco Gonzalez, Cruz, additional, Beck, Anita E., additional, Golden-Grant, Katie L., additional, Egense, Alena, additional, Parikh, Aditi, additional, Raimondi, Chantalle, additional, Angle, Brad, additional, Allen, William, additional, Schott, Suzanna, additional, Algrabli, Adi, additional, Robin, Nathaniel H., additional, Ray, Joseph W., additional, Everman, David B., additional, Gambello, Michael J., additional, and Chung, Wendy K., additional

Published
2018
Full Text
View/download PDF

47. Natural history and genotype‐phenotype correlations in 72 individuals with SATB2 ‐associated syndrome

Author

Zarate, Yuri A., primary, Smith‐Hicks, Constance L., additional, Greene, Carol, additional, Abbott, Mary‐Alice, additional, Siu, Victoria M., additional, Calhoun, Amy R. U. L., additional, Pandya, Arti, additional, Li, Chumei, additional, Sellars, Elizabeth A., additional, Kaylor, Julie, additional, Bosanko, Katherine, additional, Kalsner, Louisa, additional, Basinger, Alice, additional, Slavotinek, Anne M., additional, Perry, Hazel, additional, Saenz, Margarita, additional, Szybowska, Marta, additional, Wilson, Louise C., additional, Kumar, Ajith, additional, Brain, Caroline, additional, Balasubramanian, Meena, additional, Dubbs, Holly, additional, Ortiz‐Gonzalez, Xilma R., additional, Zackai, Elaine, additional, Stein, Quinn, additional, Powell, Cynthia M., additional, Schrier Vergano, Samantha, additional, Britt, Allison, additional, Sun, Angela, additional, Smith, Wendy, additional, Bebin, E. Martina, additional, Picker, Jonathan, additional, Kirby, Amelia, additional, Pinz, Hailey, additional, Bombei, Hannah, additional, Mahida, Sonal, additional, Cohen, Julie S., additional, Fatemi, Ali, additional, Vernon, Hilary J., additional, McClellan, Rebecca, additional, Fleming, Leah R., additional, Knyszek, Brittney, additional, Steinraths, Michelle, additional, Velasco Gonzalez, Cruz, additional, Beck, Anita E., additional, Golden‐Grant, Katie L., additional, Egense, Alena, additional, Parikh, Aditi, additional, Raimondi, Chantalle, additional, Angle, Brad, additional, Allen, William, additional, Schott, Suzanna, additional, Algrabli, Adi, additional, Robin, Nathaniel H., additional, Ray, Joseph W., additional, Everman, David B., additional, Gambello, Michael J., additional, and Chung, Wendy K., additional

Published
2018
Full Text
View/download PDF

48. Diagnostic value of exome and whole genome sequencing in craniosynostosis

Author

Miller, Kerry A, Twigg, Stephen R F, McGowan, Simon J, Phipps, Julie M, Fenwick, Aimée L, Johnson, David, Wall, Steven A, Noons, Peter, Rees, Katie E M, Tidey, Elizabeth A, Craft, Judith, Taylor, John, Taylor, Jenny C, Goos, Jacqueline A C, Swagemakers, Sigrid M A, Mathijssen, Irene M J, van der Spek, Peter J, Lord, Helen, Lester, Tracy, Abid, Noina, Cilliers, Deirdre, Hurst, Jane A, Morton, Jenny E V, Sweeney, Elizabeth, Weber, Astrid, Wilson, Louise C, Wilkie, Andrew O M, Plastic and Reconstructive Surgery and Hand Surgery, and Pathology

Subjects
Developmental Defects, Genome, Human, Exome/whole genome sequencing, High-Throughput Nucleotide Sequencing, Neoplasm Proteins, Craniosynostoses, Predictive Value of Tests, Craniosynostosis, Mutation, Humans, Exome, Genetic Testing, Actionable mutation
Abstract

Background. Craniosynostosis, the premature fusion of one or more cranial sutures, occurs in ~1 in 2250 births, either in isolation or as part of a syndrome. Mutations in at least 57 genes have been associated with craniosynostosis, but only a minority of these are included in routine laboratory genetic testing. Methods. We utilised exome or whole genome sequencing to seek a genetic cause in a cohort of 40 subjects with craniosynostosis, selected by clinical or molecular geneticists as being high priority cases, and in whom prior clinically-driven genetic testing had been negative. Results. We identified likely associated mutations in 15 patients (37.5%), involving 14 different genes. All genes were mutated in single families, except for IL11RA (2 families). We classified the other positive diagnoses as follows: commonly mutated craniosynostosis genes with atypical presentation (EFNB1, TWIST1); other core craniosynostosis genes (CDC45, MSX2, ZIC1); genes for which mutations are only rarely associated with craniosynostosis (FBN1, HUWE1, KRAS, STAT3); and known disease genes for which a causal relationship with craniosynostosis is currently unknown (AHDC1, NTRK2). In two further families, likely novel disease genes are currently undergoing functional validation. In 5 of the 15 positive cases, the (previously unanticipated) molecular diagnosis had immediate, actionable consequences for either genetic or medical management (mutations in EFNB1, FBN1, KRAS, NTRK2, STAT3). Conclusions. This substantial genetic heterogeneity, and the multiple actionable mutations identified, emphasises the benefits of exome/whole genome sequencing to identify causal mutations in craniosynostosis cases for which routine clinical testing has yielded negative results.

Published
2016

49. Autosomal dominant frontometaphyseal dysplasia: Delineation of the clinical phenotype

Author

Wade, Emma M., primary, Jenkins, Zandra A., additional, Daniel, Philip B., additional, Morgan, Tim, additional, Addor, Marie C., additional, Adés, Lesley C., additional, Bertola, Debora, additional, Bohring, Axel, additional, Carter, Erin, additional, Cho, Tae‐Joon, additional, de Geus, Christa M., additional, Duba, Hans‐Christoph, additional, Fletcher, Elaine, additional, Hadzsiev, Kinga, additional, Hennekam, Raoul C. M., additional, Kim, Chong A., additional, Krakow, Deborah, additional, Morava, Eva, additional, Neuhann, Teresa, additional, Sillence, David, additional, Superti‐Furga, Andrea, additional, Veenstra‐Knol, Hermine E., additional, Wieczorek, Dagmar, additional, Wilson, Louise C., additional, Markie, David M., additional, and Robertson, Stephen P., additional

Published
2017
Full Text
View/download PDF

50. Mutations in PROSC Disrupt Cellular Pyridoxal Phosphate Homeostasis and Cause Vitamin-B6-Dependent Epilepsy

Author

Darin, Niklas, primary, Reid, Emma, additional, Prunetti, Laurence, additional, Samuelsson, Lena, additional, Husain, Ralf A., additional, Wilson, Matthew, additional, El Yacoubi, Basma, additional, Footitt, Emma, additional, Chong, W.K., additional, Wilson, Louise C., additional, Prunty, Helen, additional, Pope, Simon, additional, Heales, Simon, additional, Lascelles, Karine, additional, Champion, Mike, additional, Wassmer, Evangeline, additional, Veggiotti, Pierangelo, additional, de Crécy-Lagard, Valérie, additional, Mills, Philippa B., additional, and Clayton, Peter T., additional

Published
2016
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results