Journal article
Loss-of-function HDAC8 mutations cause a phenotypic spectrum of Cornelia de Lange syndrome-like features, ocular hypertelorism, large fontanelle and X-linked inheritance
FJ Kaiser, M Ansari, D Braunholz, MC Gil-Rodríguez, C Decroos, JJ Wilde, CT Fincher, M Kaur, M Bando, DJ Amor, PS Atwal, M Bahlo, CM Bowman, JJ Bradley, HG Brunner, D Clark, MD Campo, N Di Donato, P Diakumis, H Dubbs Show all
Human Molecular Genetics | Published : 2014
DOI: 10.1093/hmg/ddu002
Abstract
Cornelia de Lange syndrome (CdLS) is amultisystemgenetic 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 individ..
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Awarded by Australian Research Council
Funding Acknowledgements
This work was supported by National Institutes of Health Grants (NICHD K08HD055488 to, M. A. D., (GM49758 to D. W. C., NICHD P01 HD052860 to I. D. K.; research grants from the USA CdLS Foundation; the Doris Duke Charitable Foundation to M. A. D.; institutional funds from the Children's Hospital of Philadelphia; the Roy & Diana Vagelos Scholars Program in Molecular Life Sciences at the University of Pennsylvania; intramural funding from the University of Lubeck (Schwerpunktprogramm, Medizinische Genetik: Von seltenen Varianten zur Krankheitsentstehung) to F.J.K.; the German Federal Ministry of Education and Research (B.M.B.F.) under the frame of E-Rare-2 (TARGET-CdLS to F.J.K.); the ERA-Net for Research on Rare Diseases, Research Program of Innovative Cell Biology by Innovative Technology and Grant-in-Aid for Scientific Research to K. S.; the Region of Tuscany to A. M.; the UK Medical Research Council to D. R. F. and M. A.; the Spanish Ministry of Health Fondo de Investigacion Sanitaria (FIS) [PI12/01318]; the Diputacion General de Aragon (Grupo Consolidado B20); CIBERER (GCV-HCULB Zaragoza); the European Social Fund to J.P.; the Australian Research Council to M. B., the National Health and Medical Research Council to M. B., the Victorian Government's Operational Infrastructure Support Program, as well as Australian Government National Health and Medical Research Council IRIISS support to M. B. and P. D. Sequencing was provided by the University of Washington Center for Mendelian Genomics (UW CMG) and was funded by the National Human Genome Research Institute and the National Heart, Lung and Blood Institute grant (1U54HG006493 to Drs Debbie Nickerson, Jay Shendure and Michael Bamshad). Work was performed under the FORGE Canada and Care4Rare Canada Consortiums funded by Genome Canada, the Canadian Institutes of Health Research, the Ontario Genomics Institute (OGI-049), Ontario Research Fund, Genome Quebec, Genome British Columbia and CHEO Foundation.