Dataset Information

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

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Data on unpublished and published cases were collected through the PURA Syndrome Foundation and the literature.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.

SUBMITTER: Johannesen KM

PROVIDER: S-EPMC8592566 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Publications

<i>PURA-</i>Related Developmental and Epileptic Encephalopathy: Phenotypic and Genotypic Spectrum.

Johannesen Katrine M KM Gardella Elena E Gjerulfsen Cathrine E CE Bayat Allan A Rouhl Rob P W RPW Reijnders Margot M Whalen Sandra S Keren Boris B Buratti Julien J Courtin Thomas T Wierenga Klaas J KJ Isidor Bertrand B Piton Amélie A Faivre Laurence L Garde Aurore A Moutton Sébastien S Tran-Mau-Them Frédéric F Denommé-Pichon Anne-Sophie AS Coubes Christine C Larson Austin A Esser Michael J MJ Appendino Juan Pablo JP Al-Hertani Walla W Gamboni Beatriz B Mampel Alejandra A Mayorga Lía L Orsini Alessandro A Bonuccelli Alice A Suppiej Agnese A Van-Gils Julien J Vogt Julie J Damioli Simona S Giordano Lucio L Moortgat Stephanie S Wirrell Elaine E Hicks Sarah S Kini Usha U Noble Nathan N Stewart Helen H Asakar Shailesh S Cohen Julie S JS Naidu SakkuBai R SR Collier Ashley A Brilstra Eva H EH Li Mindy H MH Brew Casey C Bigoni Stefania S Ognibene Davide D Ballardini Elisa E Ruivenkamp Claudia C Faggioli Raffaella R Afenjar Alexandra A Rodriguez Diana D Bick David D Segal Devorah D Coman David D Gunning Boudewijn B Devinsky Orrin O Demmer Laurie A LA Grebe Theresa T Pruna Dario D Cursio Ida I Greenhalgh Lynn L Graziano Claudio C Singh Rahul Raman RR Cantalupo Gaetano G Willems Marjolaine M Yoganathan Sangeetha S Góes Fernanda F Leventer Richard J RJ Colavito Davide D Olivotto Sara S Scelsa Barbara B Andrade Andrea V AV Ratke Kelly K Tokarz Farha F Khan Atiya S AS Ormieres Clothilde C Benko William W Keough Karen K Keros Sotirios S Hussain Shanawaz S Franques Ashlea A Varsalone Felicia F Grønborg Sabine S Mignot Cyril C Heron Delphine D Nava Caroline C Isapof Arnaud A Borlot Felippe F Whitney Robyn R Ronan Anne A Foulds Nicola N Somorai Marta M Brandsema John J Helbig Katherine L KL Helbig Ingo I Ortiz-González Xilma R XR Dubbs Holly H Vitobello Antonio A Anderson Mel M Spadafore Dominic D Hunt David D Møller Rikke S RS Rubboli Guido G

Neurology. Genetics 20211115 6

<h4>Background and objectives</h4>Purine-rich element-binding protein A (<i>PURA</i>) gene encodes Pur-α, a conserved protein essential for normal postnatal brain development. Recently, a <i>PURA</i> 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 <i>PURA</i> syndrome by collecting data, including EEG, from a large cohort of affected patients.<h4>Methods</h4>Da ...[more]

PMID: 34790866