1. MED27 Variants Cause Developmental Delay, Dystonia, and Cerebellar Hypoplasia
- Author
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Lydie Burglen, Michael F. Wangler, Leila Qebibo, Dimitri Krainc, Hilde Van Esch, Niccolo E. Mencacci, Pascal Joset, Henry Houlden, Christopher Carroll, Claudia Ravelli, Frances A. High, Linyan Meng, Jill V. Hunter, Anu Suomalainen, Dana Marafi, Shen Gu, Katleen Ballon, Scott E. Hickey, Nebal Waill Saadi, Yunru Shao, Bernabé I. Bustos, James R. Lupski, Pirjo Isohanni, Stephanie M. Brooks, Paulina Gonzalez-Latapi, Fatima Rahman, Reza Maroofian, Chiara De Luca, Stephanie Efthymiou, Jasem Y. Al-Hashel, Tadahiro Mitani, Steven J. Lubbe, Brett H. Graham, Yavuz Sahin, Katharina Steindl, Shazia Maqbool, Davut Pehlivan, Alejandro V. Hernandez, Amy Armstrong-Javors, Daniel G. Calame, Annette Hackenberg, Jennifer E. Posey, Anita Rauch, Walaa A. Kamel, Yaping Yang, HUS Children and Adolescents, Research Programs Unit, Anu Wartiovaara / Principal Investigator, Children's Hospital, Clinicum, STEMM - Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, Lastenneurologian yksikkö, Helsinki University Hospital Area, HUS Helsinki and Uusimaa Hospital District, and FinMIT Centre of Excellence (Wartiovaara Anu)
- Subjects
0301 basic medicine ,Adult ,Cerebellum ,Adolescent ,Developmental Disabilities ,Biology ,Nervous System Malformations ,3124 Neurology and psychiatry ,Cataract ,03 medical and health sciences ,0302 clinical medicine ,Mediator ,Intellectual disability ,Exome Sequencing ,medicine ,Humans ,Global developmental delay ,Amino Acid Sequence ,Child ,Cerebellar hypoplasia ,Exome sequencing ,Dystonia ,Genetics ,Epilepsy ,Mediator Complex ,3112 Neurosciences ,Genetic Variation ,Infant ,medicine.disease ,3. Good health ,030104 developmental biology ,medicine.anatomical_structure ,Phenotype ,Neurology ,Child, Preschool ,Neurology (clinical) ,Neural development ,030217 neurology & neurosurgery - Abstract
The Mediator multiprotein complex functions as a regulator of RNA polymerase II-catalyzed gene transcription. In this study, exome sequencing (ES) detected biallelic putative disease-causing variants in MED27, encoding Mediator Complex Subunit 27, in sixteen patients from eleven families with a novel neurodevelopmental syndrome. Patient phenotypes are highly homogeneous including global developmental delay, intellectual disability, axial hypotonia with distal spasticity, dystonic movements, and cerebellar hypoplasia. Seizures and cataracts were noted in severely affected individuals. Identification of multiple patients with biallelic MED27 variants supports the critical role of MED27 in normal human neural development, particularly for the cerebellum. This article is protected by copyright. All rights reserved.
- Published
- 2021