Journal article
ACTB Loss-of-Function Mutations Result in a Pleiotropic Developmental Disorder
S Cuvertino, HM Stuart, KE Chandler, NA Roberts, R Armstrong, L Bernardini, S Bhaskar, B Callewaert, J Clayton-Smith, CH Davalillo, C Deshpande, K Devriendt, MC Digilio, A Dixit, M Edwards, JM Friedman, A Gonzalez-Meneses, S Joss, B Kerr, AK Lampe Show all
American Journal of Human Genetics | CELL PRESS | Published : 2017
Open access
Abstract
ACTB encodes β-actin, an abundant cytoskeletal housekeeping protein. In humans, postulated gain-of-function missense mutations cause Baraitser-Winter syndrome (BRWS), characterized by intellectual disability, cortical malformations, coloboma, sensorineural deafness, and typical facial features. To date, the consequences of loss-of-function ACTB mutations have not been proven conclusively. We describe heterozygous ACTB deletions and nonsense and frameshift mutations in 33 individuals with developmental delay, apparent intellectual disability, increased frequency of internal organ malformations (including those of the heart and the renal tract), growth retardation, and a recognizable facial ge..
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Awarded by National Institute on Disability and Rehabilitation Research
Funding Acknowledgements
We are thankful to all individual and their families for participating in the study. We acknowledge the support of the Newlife Foundation (S.B., SG/L4-L5l01 and 16-17/10; and A.S.W., 15-16/03) and Medical Research Council UK (L002744/1). We are grateful to the Scales family and friends for supporting S.C. through the Central Manchester University Hospitals NHS Foundation Trust, Kabuki Research Fund number 629396. N.A.R. is supported by a Kidney Research UK fellowship. H.M.S. is supported by NIHR Lecturer award and the Academy of Medical Sciences. R.L. is supported by a Wellcome Trust Senior Clinical Fellowship. B.C. is a senior clinical investigator of the Fund for Scientific Research-Flanders. We thank Prof. Susan Kimber for providing laboratory space to conduct some of the experiments. The Deciphering Developmental Disorders study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). The views expressed in this publication are those of the author(s) and not necessarily those of the Wellcome Trust or the Department of Health. The study has UK Research Ethics Committee approval (10/H0305/83, granted by the Cambridge South REC, and GEN/284/12 granted by the Republic of Ireland REC). The research team acknowledges the support of the National Institute for Health Research, through the Comprehensive Clinical Research Network. None of the authors have any conflicts of interests to declare.