@article{483384fd39c443f59a7b21b371c56e98,
title = "MED27 Variants Cause Developmental Delay, Dystonia, and Cerebellar Hypoplasia",
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.",
author = "Linyan Meng and Pirjo Isohanni and Yunru Shao and Graham, {Brett H.} and Hickey, {Scott E.} and Stephanie Brooks and Anu Suomalainen and Pascal Joset and Katharina Steindl and Anita Rauch and Annette Hackenberg and High, {Frances A.} and Amy Armstrong-Javors and Mencacci, {Niccol{\`o} E.} and Paulina Gonz{\`a}lez-Latapi and Kamel, {Walaa A.} and Al-Hashel, {Jasem Y.} and Bustos, {Bernab{\'e} I.} and Hernandez, {Alejandro V.} and Dimitri Krainc and Lubbe, {Steven J.} and {Van Esch}, Hilde and {De Luca}, Chiara and Katleen Ballon and Claudia Ravelli and Lydie Burglen and Leila Qebibo and Calame, {Daniel G.} and Tadahiro Mitani and Dana Marafi and Davut Pehlivan and Saadi, {Nebal W.} and Yavuz Sahin and Reza Maroofian and Stephanie Efthymiou and Henry Houlden and Shazia Maqbool and Fatima Rahman and Shen Gu and Posey, {Jennifer E.} and Lupski, {James R.} and Hunter, {Jill V.} and Wangler, {Michael F.} and Carroll, {Christopher J.} and Yaping Yang",
note = "Funding Information: N.E.M. is supported by a Parkinson's Foundation grant. P.I. is supported by the Foundation for Pediatric Research. D.K. is supported by the Simpson Querrey Center for Neurogenetics. Biospecimens used in the analyses presented in this article were obtained from the Northwestern University Movement Disorders Center (MDC) Biorepository. As such, the investigators within MDC Biorepository contributed to the design and implementation of the MDC Biorepository and/or provided data and collected biospecimens but did not participate in the analysis or writing of this report. MDC Biorepository investigators include Tanya Simuni, MD; Dimitri Krainc, MD, PhD; Opal Puneet, MD, PhD; Cindy Zadikoff, MD; Onur Melen, MD; Danny Bega, MD; Roneil G. Malkani, MD; Steven Lubbe, PhD; Niccolo E. Mencacci, MD, PhD; Christina Zelano, PhD; Joanna Blackburn, MD; Firas Wehbe, MD, PhD; Lisa Kinsley, MS, CGC; and Tina Ward, MS. A gift from the Malkin family generously supported the work of the MDC Biorepository. J.R.L. is supported by a grant from the National Human Genome Research Institute (NHGRI) and National Heart, Lung, and Blood Institute (NHLBI) to the Baylor–Hopkins Center for Mendelian Genomics (UM1 HG006542); a National Institute of Neurological Disorders and Stroke grant (R35NS105078); and an Muscular Dystrophy Association grant (512848). T.M. is supported by the Uehara Memorial Foundation. D.M. is supported by a Medical Genetics Research Fellowship Program through the National Institute of General Medical Sciences (NIGMS) at US NIH (T32 GM007526‐42). D.P. is supported by a Clinical Research Training Scholarship in Neuromuscular Disease partnered by the American Brain Foundation and Muscle Study Group, and the International Rett Syndrome Foundation (grant #3701‐1). J.E.P. was supported by NHGRI K08 HG008986. Funding Information: N.E.M. is supported by a Parkinson's Foundation grant. P.I. is supported by the Foundation for Pediatric Research. D.K. is supported by the Simpson Querrey Center for Neurogenetics. Biospecimens used in the analyses presented in this article were obtained from the Northwestern University Movement Disorders Center (MDC) Biorepository. As such, the investigators within MDC Biorepository contributed to the design and implementation of the MDC Biorepository and/or provided data and collected biospecimens but did not participate in the analysis or writing of this report. MDC Biorepository investigators include Tanya Simuni, MD; Dimitri Krainc, MD, PhD; Opal Puneet, MD, PhD; Cindy Zadikoff, MD; Onur Melen, MD; Danny Bega, MD; Roneil G. Malkani, MD; Steven Lubbe, PhD; Niccolo E. Mencacci, MD, PhD; Christina Zelano, PhD; Joanna Blackburn, MD; Firas Wehbe, MD, PhD; Lisa Kinsley, MS, CGC; and Tina Ward, MS. A gift from the Malkin family generously supported the work of the MDC Biorepository. J.R.L. is supported by a grant from the National Human Genome Research Institute (NHGRI) and National Heart, Lung, and Blood Institute (NHLBI) to the Baylor?Hopkins Center for Mendelian Genomics (UM1 HG006542); a National Institute of Neurological Disorders and Stroke grant (R35NS105078); and an Muscular Dystrophy Association grant (512848). T.M. is supported by the Uehara Memorial Foundation. D.M. is supported by a Medical Genetics Research Fellowship Program through the National Institute of General Medical Sciences (NIGMS) at US NIH (T32 GM007526-42). D.P. is supported by a Clinical Research Training Scholarship in Neuromuscular Disease partnered by the American Brain Foundation and Muscle Study Group, and the International Rett Syndrome Foundation (grant #3701-1). J.E.P. was supported by NHGRI K08 HG008986. We thank the Finnish Institute for Molecular Medicine for whole-exome sequencing, and A. Harju and M. Pohjanpelto for technical assistance. Publisher Copyright: {\textcopyright} 2021 American Neurological Association",
year = "2021",
month = apr,
doi = "10.1002/ana.26019",
language = "English (US)",
volume = "89",
pages = "828--833",
journal = "Annals of neurology",
issn = "0364-5134",
publisher = "John Wiley and Sons Inc.",
number = "4",
}
