Journal article

RAD21 Mutations Cause a Human Cohesinopathy

Matthew A Deardorff, Jonathan J Wilde, Melanie Albrecht, Emma Dickinson, Stephanie Tennstedt, Diana Braunholz, Maren Moennich, Yuqian Yan, Weizhen Xu, Maria Concepcion Gil-Rodriguez, Dinah Clark, Hakon Hakonarson, Sara Halbach, Laura Daniela Michelis, Abhinav Rampuria, Eva Rossier, Stephanie Spranger, Lionel Van Maldergem, Sally Ann Lynch, Gabriele Gillessen-Kaesbach Show all

AMERICAN JOURNAL OF HUMAN GENETICS | CELL PRESS | Published : 2012

Abstract

The evolutionarily conserved cohesin complex was originally described for its role in regulating sister-chromatid cohesion during mitosis and meiosis. Cohesin and its regulatory proteins have been implicated in several human developmental disorders, including Cornelia de Lange (CdLS) and Roberts syndromes. Here we show that human mutations in the integral cohesin structural protein RAD21 result in a congenital phenotype consistent with a "cohesinopathy." Children with RAD21 mutations display growth retardation, minor skeletal anomalies, and facial features that overlap findings in individuals with CdLS. Notably, unlike children with mutations in NIPBL, SMC1A, or SMC3, these individuals have ..

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Grants

Awarded by National Institutes of Health from the National Institute of Child Health and Human Development [NICHD]


Awarded by Cancer Council Victoria Australia


Awarded by Australian National Health and Medical Research Council


Awarded by Marsden grant


Awarded by Spanish Ministerio de Sanidad


Awarded by EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT


Awarded by EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH &HUMAN DEVELOPMENT


Funding Acknowledgements

We are exceptionally grateful to the children and families who participated in this study as well as to the referring physicians and colleagues who have contributed samples and clinical information. We thank Maninder Kaur and Melanie Hullings for technical assistance and Pavel Lobachevsky and Goli Mostoufi-Moab for assistance with statistical analysis of the radiation-survival experiments. We are indebted to the continued support of the USA and International Cornelia de Lange Syndrome Foundations. This work was supported by National Institutes of Health grants K08HD055488 (from the National Institute of Child Health and Human Development [NICHD] to M.A.D.), P01 HD052860 (from the NICHD to I.D.K.), research grants from the USA CdLS Foundation, institutional funds from the Children's Hospital of Philadelphia, Cancer Council Victoria Australia grant 081219 (to H.X. and M.J.M.), Australian National Health and Medical Research Council project grant 1007659 (to R.G.R., H.X., and M.J.M.), Marsden grant UOO0713 (to E.D., M.M., and J.H.), funds from New Zealand Lottery Health Research (to E.D., MM., and J.H.), Spanish Ministerio de Sanidad grant PI091422 (to M.C.G.-R.), and intramural funding of the University of Lubeck, Germany ("Schwerpunktprogramm: Medizinische Genetik," to F.J.K. and G.G.-K.).