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of PURA syndrome by collecting data, including EEG, from a large cohort of affected patients.; Methods: Data on unpublished and published cases were collected through the PURA Syndrome Foundation and the literature.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. (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)eCollection. Cited Medium: Print. NLM ISO Abbr: Neurol Genet. PubMed Central ID: PMC8592566. Linked References: Epileptic Disord. 2019 Jun 1;21(S1):41-47. (PMID: 31149903); Epilepsia. 2020 Jun;61(6):1234-1239. (PMID: 32427350); Brain. 2019 Aug 1;142(8):2303-2318. (PMID: 31302675); Dev Med Child Neurol. 2009 Jan;51(1):30-8. (PMID: 19087102); Am J Hum Genet. 2013 Sep 5;93(3):496-505. (PMID: 23993195); Epilepsia. 2017 Apr;58(4):522-530. (PMID: 28276060); Orthod Craniofac Res. 2009 Aug;12(3):212-20. (PMID: 19627523); Lancet Neurol. 2006 Jun;5(6):513-24. (PMID: 16713923); Epilepsia. 2011 Oct;52(10):1828-34. (PMID: 21770924); Clin Genet. 2016 May;89(5):557-63. (PMID: 26663098); Elife. 2014 Jun 24;3:e02020. (PMID: 24963138); Nucleic Acids Res. 2010 Jan;38(Database issue):D492-6. (PMID: 19854944); Am J Med Genet A. 2018 Jan;176(1):56-67. (PMID: 29150892); Obstet Gynecol. 2017 Jun;129(6):1037-1039. (PMID: 28486374); Neurology. 2018 Sep 18;91(12):e1112-e1124. (PMID: 30171078); Congenit Anom (Kyoto). 2017 Nov;57(6):201-204. (PMID: 28164378); Eur J Med Genet. 2019 Feb;62(2):103-108. (PMID: 29908350); Neuroscience. 2016 Nov 19;337:177-190. (PMID: 27651147); BMC Genet. 2018 Jul 6;19(1):40. (PMID: 29976148); J Med Genet. 2018 Feb;55(2):104-113. (PMID: 29097605); Epilepsy Res. 2018 Jul;143:79-81. (PMID: 29677576); Brain Dev. 2016 Mar;38(3):285-92. (PMID: 26482601); J Hum Genet. 2017 Feb;62(2):185-189. (PMID: 27535030); Am J Hum Genet. 2019 May 2;104(5):948-956. (PMID: 30982612); Genet Med. 2015 May;17(5):405-24. (PMID: 25741868); J Med Genet. 2014 Dec;51(12):806-13. (PMID: 25342064); Pediatr Neurol. 2020 Mar;104:62-63. (PMID: 31911028); Neurology. 2016 May 10;86(19):1794-800. (PMID: 27029630); Mol Genet Metab. 2018 Mar;123(3):331-336. (PMID: 29307761); Epilepsia. 2017 Apr;58(4):512-521. (PMID: 28276062); Mol Cell Biol. 2003 Oct;23(19):6857-75. (PMID: 12972605); Am J Med Genet A. 2013 Oct;161A(10):2604-8. (PMID: 23950017); J Cell Physiol. 2013 Jan;228(1):65-72. (PMID: 22553010); Cold Spring Harb Mol Case Stud. 2015 Oct;1(1):a000356. (PMID: 27148565); Mov Disord. 2010 Aug 15;25(11):1538-49. (PMID: 20589866); J Genet. 2020;99:. (PMID: 32089526); Hum Mol Genet. 2012 Feb 1;21(3):473-84. (PMID: 22010047); Epilepsy Res. 2016 Dec;128:43-47. (PMID: 27810515); Mol Cytogenet. 2015 Nov 14;8:89. (PMID: 26582469); Elife. 2016 Jan 08;5:. (PMID: 26744780); Am J Hum Genet. 2014 Nov 6;95(5):579-83. (PMID: 25439098). Linking ISSN: 23767839. Subset: PubMed not MEDLINE; Date of Electronic Publication: 2021 Nov 15. ; Original Imprints: Publication: [Hagerstown, MD] : Published for the American Academy of Neurology by Wolters Kluwer, [2015]- <br />