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 Larson; Michael 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; Sakkubai R Naidu; Ashley Collier; Eva H Brilstra; Mindy H Li; Casey Brew; Stefania Bigoni; Davide Ognibene; Elisa Ballardini; Claudia Ruivenkamp; Raffaella Faggioli; Alexandra Afenjar; Diana Rodriguez; David Bick; Devorah Segal; David Coman; Boudewijn Gunning; Orrin Devinsky; Laurie A Demmer; Theresa Grebe; Dario Pruna; Ida Cursio; Lynn Greenhalgh; Claudio Graziano; Rahul Raman Singh; Gaetano Cantalupo; Marjolaine Willems; Sangeetha Yoganathan; Fernanda Góes; Richard J Leventer; Davide Colavito; Sara Olivotto; Barbara Scelsa; Andrea V Andrade; Kelly Ratke; Farha Tokarz; Atiya S Khan; Clothilde Ormieres; William Benko; Karen Keough; Sotirios Keros; Shanawaz Hussain; Ashlea Franques; Felicia Varsalone; Sabine Grønborg; Cyril Mignot; Delphine Heron; Caroline Nava; Arnaud Isapof; Felippe Borlot; Robyn Whitney; Anne Ronan; Nicola Foulds; Marta Somorai; John Brandsema; Katherine L Helbig; Ingo Helbig; Xilma R Ortiz-González; Holly Dubbs; Antonio Vitobello; Mel Anderson; Dominic Spadafore; David Hunt; Rikke S Møller; Guido Rubboli

doi:10.1212/nxg.0000000000000613

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

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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, …

Neurology Genetics, Vol.7(6)

15/11/2021

DOI: https://doi.org/10.1212/nxg.0000000000000613

PMCID: PMC8592566

PMID: 34790866

Abstract

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.

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Title: PURA- Related Developmental and Epileptic Encephalopathy: Phenotypic and Genotypic Spectrum
Creators - without role: Katrine M Johannesen - University of Southern Denmark
Elena Gardella - University of Southern Denmark
Cathrine E Gjerulfsen - Filadelfia
Allan Bayat - University of Southern Denmark
Rob P W Rouhl - University of Southern Denmark
Margot Reijnders
Sandra Whalen - University of Southern Denmark
Boris Keren - University of Southern Denmark
Julien Buratti - University of Southern Denmark
Thomas Courtin - University of Southern Denmark
Klaas J Wierenga - University of Southern Denmark
Bertrand Isidor - Filadelfia
Amélie Piton - University of Southern Denmark
Laurence Faivre - University of Southern Denmark
Aurore Garde - University of Southern Denmark
Sébastien Moutton - University of Southern Denmark
Frédéric Tran-Mau-Them - Equipe GAD (LNC - U1231)
Anne-Sophie Denommé-Pichon - Université Bourgogne Franche-Comté
Christine Coubes - University of Southern Denmark
Austin Larson - University of Southern Denmark
Michael J Esser - University of Southern Denmark
Juan Pablo Appendino - University of Southern Denmark
Walla Al-Hertani - University of Southern Denmark
Beatriz Gamboni - University of Southern Denmark
Alejandra Mampel - University of Southern Denmark
Lía Mayorga - University of Southern Denmark
Alessandro Orsini - Filadelfia
Alice Bonuccelli - University of Southern Denmark
Agnese Suppiej - University of Southern Denmark
Julien Van-Gils - University of Southern Denmark
Julie Vogt - University of Southern Denmark
Simona Damioli - Filadelfia
Lucio Giordano - University of Southern Denmark
Stephanie Moortgat - University of Southern Denmark
Elaine Wirrell - University of Southern Denmark
Sarah Hicks - University of Southern Denmark
Usha Kini - University of Southern Denmark
Nathan Noble - University of Southern Denmark
Helen Stewart - University of Southern Denmark
Shailesh Asakar - University of Southern Denmark
Julie S Cohen - Filadelfia
Sakkubai R Naidu - University of Southern Denmark
Ashley Collier - University of Southern Denmark
Eva H Brilstra - University of Southern Denmark
Mindy H Li - Filadelfia
Casey Brew - University of Southern Denmark
Stefania Bigoni - University of Southern Denmark
Davide Ognibene - University of Southern Denmark
Elisa Ballardini - University of Southern Denmark
Claudia Ruivenkamp - University of Southern Denmark
Raffaella Faggioli - University of Southern Denmark
Alexandra Afenjar - University of Southern Denmark
Diana Rodriguez - University of Southern Denmark
David Bick - University of Southern Denmark
Devorah Segal - University of Southern Denmark
David Coman - University of Southern Denmark
Boudewijn Gunning - Filadelfia
Orrin Devinsky - University of Southern Denmark
Laurie A Demmer - Filadelfia
Theresa Grebe - University of Southern Denmark
Dario Pruna - University of Southern Denmark
Ida Cursio - University of Southern Denmark
Lynn Greenhalgh - University of Southern Denmark
Claudio Graziano - University of Southern Denmark
Rahul Raman Singh - Filadelfia
Gaetano Cantalupo - University of Southern Denmark
Marjolaine Willems - University of Southern Denmark
Sangeetha Yoganathan - Filadelfia
Fernanda Góes
Richard J Leventer - University of Southern Denmark
Davide Colavito - Filadelfia
Sara Olivotto - University of Southern Denmark
Barbara Scelsa - Filadelfia
Andrea V Andrade - University of Southern Denmark
Kelly Ratke - University of Southern Denmark
Farha Tokarz - Filadelfia
Atiya S Khan - University of Southern Denmark
Clothilde Ormieres - University of Southern Denmark
William Benko - Filadelfia
Karen Keough - University of Southern Denmark
Sotirios Keros - University of Southern Denmark
Shanawaz Hussain - Filadelfia
Ashlea Franques - University of Southern Denmark
Felicia Varsalone - University of Southern Denmark
Sabine Grønborg - University of Southern Denmark
Cyril Mignot - University of Southern Denmark
Delphine Heron - University of Southern Denmark
Caroline Nava - University of Southern Denmark
Arnaud Isapof - University of Southern Denmark
Felippe Borlot - University of Southern Denmark
Robyn Whitney - University of Southern Denmark
Anne Ronan - Filadelfia
Nicola Foulds - University of Southern Denmark
Marta Somorai - University of Southern Denmark
John Brandsema - University of Southern Denmark
Katherine L Helbig - Filadelfia
Ingo Helbig - University of Southern Denmark
Xilma R Ortiz-González - University of Southern Denmark
Holly Dubbs - University of Southern Denmark
Antonio Vitobello - University of Southern Denmark
Mel Anderson - Filadelfia
Dominic Spadafore - Filadelfia
David Hunt - Filadelfia
Rikke S Møller - University of Southern Denmark
Guido Rubboli - Filadelfia
Publication Details: Neurology Genetics, Vol.7(6)
Identifiers: 9940263309311
Academic Unit: Physiologie et Médecine Expérimentale du coeur et des muscles - PhyMedExp
Language: English
Resource Type: Journal article
Local Fields: hal-03881856