MED27 Variants Cause Developmental Delay, Dystonia, and Cerebellar Hypoplasia.

TitleMED27 Variants Cause Developmental Delay, Dystonia, and Cerebellar Hypoplasia.
Publication TypeJournal Article
Year of Publication2021
AuthorsMeng, L, Isohanni, P, Shao, Y, Graham, BH, Hickey, SE, Brooks, S, Suomalainen, A, Joset, P, Steindl, K, Rauch, A, Hackenberg, A, High, FA, Armstrong-Javors, A, Mencacci, NE, Gonzàlez-Latapi, P, Kamel, WA, Al-Hashel, JY, Bustos, BI, Hernandez, AV, Krainc, D, Lubbe, SJ, Van Esch, H, De Luca, C, Ballon, K, Ravelli, C, Burglen, L, Qebibo, L, Calame, DG, Mitani, T, Marafi, D, Pehlivan, D, Saadi, NW, Sahin, Y, Maroofian, R, Efthymiou, S, Houlden, H, Maqbool, S, Rahman, F, Gu, S, Posey, JE, Lupski, JR, Hunter, JV, Wangler, MF, Carroll, CJ, Yang, Y
JournalAnn Neurol
Date Published2021 Apr
KeywordsAdolescent, Adult, Amino Acid Sequence, Cataract, Cerebellum, Child, Child, Preschool, Developmental Disabilities, Dystonia, Epilepsy, Exome Sequencing, Genetic Variation, Humans, Infant, Mediator Complex, Nervous System Malformations, Phenotype

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.

Alternate JournalAnn Neurol
PubMed ID33443317
Grant ListT32 GM007526-42 / / United States National Institute of Health /
K08 HG008986 / HG / NHGRI NIH HHS / United States
UM1 HG006542 / HG / NHGRI NIH HHS / United States
R35NS105078 / NS / NINDS NIH HHS / United States

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