MED27 Variants Cause Developmental Delay, Dystonia, and Cerebellar Hypoplasia PMID: 33443317

ADC Targets in Oncology

2026-04-10

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

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.

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.