<scp><i>MED27</i></scp> Variants Cause Developmental Delay, Dystonia, and Cerebellar Hypoplasia
Linyan Meng, Pirjo Isohanni, Yunru Shao, Brett H. Graham, Scott E. Hickey, Stephanie Brooks, Anu Suomalainen, Pascal Joset, Katharina Steindl, Anita Rauch, Annette Hackenberg, Frances A. High, Amy Armstrong‐Javors, Niccolò E. Mencacci, Paulina González-Latapí, Walaa A. Kamel, Jasem Al-Hashel, Bernabé I. Bustos, Alejandro V. Hernandez, Dimitri Krainc, Steven Lubbe, Hilde Van Esch, Chiara De Luca, Katleen Ballon, Claudia Ravelli, Lydie Bürglen, Leila Qebibo, Daniel G. Calame, Tadahiro Mitani, Dana Marafi, Davut Pehli̇van, Nebal Waill Saadi, Yavuz Şahin, Reza Maroofian, Stéphanie Efthymiou, Henry Houlden, Shazia Maqbool, Fatima Rahman, Shen Gu, Jennifer E. Posey, James R. Lupski, Jill V. Hunter, Michael F. Wangler, Christopher J. Carroll, Yaping Yang
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.