PURA-Related Developmental and Epileptic Encephalopathy: Phenotypic and Genotypic Spectrum

Katrine M. Johannesen*, Elena Gardella, Cathrine E. Gjerulfsen, Allan Bayat, Rob P.W. Rouhl, Margot Reijnders, Sandra Whalen, Boris Keren, Julien Buratti, Thomas Courtin, Klaas J. Wierenga, Bertrand Isidor, Amélie Piton, Laurence Faivre, Aurore Garde, Sébastien Moutton, Frédéric Tran-Mau-Them, Anne Sophie Denommé-Pichon, Christine Coubes, Austin LarsonMichael J. Esser, Juan Pablo Appendino, Walla Al-Hertani, Beatriz Gamboni, Alejandra Mampel, Lía Mayorga, Alessandro Orsini, Alice Bonuccelli, Agnese Suppiej, Julien Van-Gils, Julie Vogt, Simona Damioli, Lucio Giordano, Stephanie Moortgat, Elaine Wirrell, Sarah Hicks, Usha Kini, Nathan Noble, Helen Stewart, Shailesh Asakar, Julie S. Cohen, Sakku Bai R. Naidu, Ashley Collier, Eva H. Brilstra, Mindy H. Li, Casey Brew, Stefania Bigoni, Davide Ognibene, Rikke S. Møller, Guido Rubboli, PURA study group

*Kontaktforfatter for dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

2 Downloads (Pure)


Background and Objectives Purine-rich element-binding protein A (PURA) gene encodes Pur-α, a conserved protein essential for normal postnatal brain development. Recently, a PURA syndrome characterized by intellectual disability, hypotonia, epilepsy, and dysmorphic features was suggested. The aim of this study was to define and expand the phenotypic spectrum of PURA syndrome by collecting data, including EEG, from a large cohort of affected patients. Methods Data on unpublished and published cases were collected through the PURA Syndrome Foundation and the literature. Data on clinical, genetic, neuroimaging, and neurophysiologic features were obtained. Results A cohort of 142 patients was included. Characteristics of the PURA syndrome included neonatal hypotonia, feeding difficulties, and respiratory distress. Sixty percent of the patients developed epilepsy with myoclonic, generalized tonic-clonic, focal seizures, and/or epileptic spasms. EEG showed generalized, multifocal, or focal epileptic abnormalities. Lennox-Gastaut was the most common epilepsy syndrome. Drug refractoriness was common: 33.3% achieved seizure freedom. We found 97 pathogenic variants in PURA without any clear genotype-phenotype associations. Discussion The PURA syndrome presents with a developmental and epileptic encephalopathy with characteristics recognizable from neonatal age, which should prompt genetic screening. Sixty percent have drug-resistant epilepsy with focal or generalized seizures. We collected more than 90 pathogenic variants without observing overt genotype-phenotype associations.

TidsskriftNeurology: Genetics
Udgave nummer6
Antal sider15
StatusUdgivet - 15. dec. 2021

Bibliografisk note

Funding Information:
The authors are deeply grateful for the collaboration and support from all the PURA families, and the authors wish to acknowledge the PURA foundation for their tireless work and commitment to advance the knowledge on PURA syndrome. The authors thank Diana Baralle for inclusion of patients and Dierk Niessing and Robert Janowski for their invaluable support and comments on the manuscript. The authors thank the following for their contributions to the study: Deborah Mitchell-Langlois. The authors thank Jean-François Deleuze, Anne Boland-Augé, and Robert Olaso for the collaboration CEA/JACOB/CNRGH—CHU de Dijon—Inserm.

Publisher Copyright:
Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.


Dyk ned i forskningsemnerne om 'PURA-Related Developmental and Epileptic Encephalopathy: Phenotypic and Genotypic Spectrum'. Sammen danner de et unikt fingeraftryk.