2. Academic Validation
  3. MED27 Variants Cause Developmental Delay, Dystonia, and Cerebellar Hypoplasia

MED27 Variants Cause Developmental Delay, Dystonia, and Cerebellar Hypoplasia

  • Ann Neurol. 2021 Apr;89(4):828-833. doi: 10.1002/ana.26019.
Linyan Meng 1 2,  Pirjo Isohanni 3 4,  Yunru Shao 1 5 6,  Brett H Graham 7,  Scott E Hickey 8,  Stephanie Brooks 8,  Anu Suomalainen 3,  Pascal Joset 9,  Katharina Steindl 9,  Anita Rauch 9,  Annette Hackenberg 10,  Frances A High 11 12,  Amy Armstrong-Javors 12 13,  Niccolò E Mencacci 14 15,  Paulina Gonzàlez-Latapi 14,  Walaa A Kamel 16 17,  Jasem Y Al-Hashel 16 18,  Bernabé I Bustos 14 15,  Alejandro V Hernandez 14,  Dimitri Krainc 14 15,  Steven J Lubbe 14 15,  Hilde Van Esch 19,  Chiara De Luca 19,  Katleen Ballon 20,  Claudia Ravelli 21,  Lydie Burglen 22 23,  Leila Qebibo 22,  Daniel G Calame 1 6 24,  Tadahiro Mitani 1,  Dana Marafi 1 25,  Davut Pehlivan 1 6 24,  Nebal W Saadi 26 27,  Yavuz Sahin 28,  Reza Maroofian 29,  Stephanie Efthymiou 29,  Henry Houlden 29,  Shazia Maqbool 30,  Fatima Rahman 30,  Shen Gu 31,  Jennifer E Posey 1,  James R Lupski 1 5 6 32,  Jill V Hunter 33 34,  Michael F Wangler 1 4 35,  Christopher J Carroll 3 36,  Yaping Yang 1 2
Affiliations

Affiliations

  • 1 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX.
  • 2 Baylor Genetics, Houston, TX.
  • 3 Research Programs Unit, Stem Cells and Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
  • 4 Department of Child Neurology, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
  • 5 Department of Pediatrics, Baylor College of Medicine, Houston, TX.
  • 6 Texas Children's Hospital, Houston, TX.
  • 7 Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN.
  • 8 Department of Pediatrics, Ohio State University College of Medicine, Division of Genetic and Genomic Medicine, Nationwide Children's Hospital, Columbus, OH.
  • 9 Institute of Medical Genetics, University of Zürich, Schlieren-Zürich, Switzerland.
  • 10 Department of Pediatric Neurology, University Children's Hospital Zürich, University of Zürich, Zürich, Switzerland.
  • 11 Division of Medical Genetics, Massachusetts General Hospital, Boston, MA.
  • 12 Harvard Medical School, Boston, MA.
  • 13 Department of Pediatric Neurology, Massachusetts General Hospital, Boston, MA.
  • 14 Ken and Ruth Davee Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL.
  • 15 Simpson Querrey Center for Neurogenetics, Feinberg School of Medicine, Northwestern University, Chicago, IL.
  • 16 Department of Neurology, Ibn Sina Hospital, Kuwait City, Kuwait.
  • 17 Department of Neurology, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt.
  • 18 Department of Medicine, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait.
  • 19 Center for Human Genetics, University Hospitals Leuven, Leuven, Belgium.
  • 20 Centre for Developmental Disabilities, University Hospitals Leuven, Leuven, Belgium.
  • 21 Pediatric Neurology Department, Neurogenetics Reference Center, I-motion Institute, Public Hospital Network of Paris, Sorbonne University, Armand Trousseau Hospital, Paris, France.
  • 22 Cerebellar Malformations and Congenital Diseases Reference Center and Neurogenetics Lab, Department of Genetics, Public Hospital Network of Paris, Sorbonne University, Armand Trousseau Hospital, Paris, France.
  • 23 Developmental Brain Disorders Laboratory, Imagine Institute, Paris, France.
  • 24 Division of Neurology and Developmental Neuroscience, Department of Pediatrics, Baylor College of Medicine, Houston, TX.
  • 25 Department of Pediatrics, Faculty of Medicine, Kuwait University, Safat, Kuwait.
  • 26 College of Medicine, Baghdad University, Baghdad, Iraq.
  • 27 Children Welfare Teaching Hospital, Baghdad, Iraq.
  • 28 Department of Medical Genetics, Genoks Genetic Center, Ankara, Turkey.
  • 29 Department of Neuromuscular Disorders, University College London Institute of Neurology, London, UK.
  • 30 Development and Behavioral Pediatrics Department, Institute of Child Health and Children Hospital, Lahore, Pakistan.
  • 31 School of Biomedical Sciences, Chinese University of Hong Kong, Shatin, Hong Kong SAR.
  • 32 Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX.
  • 33 Edward B. Singleton Department of Pediatric Radiology, Texas Children's Hospital, Houston, TX.
  • 34 Department of Radiology, Baylor College of Medicine, Houston, TX.
  • 35 Jan and Dan Neurological Research Institute, Texas Children's Hospital, Houston, TX.
  • 36 Molecular and Clinical Sciences Research Institute, St George's, University of London, London, United Kingdom.
PMID: 33443317 DOI: 10.1002/ana.26019
Abstract

The Mediator multiprotein complex functions as a regulator of RNA polymerase II-catalyzed gene transcription. In this study, exome sequencing detected biallelic putative disease-causing variants in MED27, encoding Mediator complex subunit 27, in 16 patients from 11 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. ANN NEUROL 2021;89:828-833.

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