Clinical Role of Codon 87 of the CYFIP2 Gene in Early Infantile Epileptic Encephalopathy: A Clinical Case Description

Da Silva Cardoso, Juliana; Gomes, Rita; Abreu, Maria; Parente Freixo, João; Falcão Reis, Cáudia; Garrido, Cristina

Publication

Clinical Role of Codon 87 of the CYFIP2 Gene in Early Infantile Epileptic Encephalopathy: A Clinical Case Description

2023-02Journal article

dc.contributor.author	Da Silva Cardoso, Juliana
dc.contributor.author	Gomes, Rita
dc.contributor.author	Abreu, Maria
dc.contributor.author	Parente Freixo, João
dc.contributor.author	Falcão Reis, Cáudia
dc.contributor.author	Garrido, Cristina
dc.date.accessioned	2024-06-18T05:56:23Z
dc.date.available	2024-06-18T05:56:23Z
dc.date.issued	2023-02
dc.description.abstract	The diagnosis of early infantile epileptic encephalopathy (EIEE) remains challenging, and next-generation sequencing (NGS) techniques have played a key role in identifying genetic causes. Recent studies have shown an association between mutations in the CYFIP2 gene and EIEE, with 20 deleterious variants reported so far and a de novo mutational hotspot at codon 87. A male infant presented with seizures since the age of four months as well as significant developmental delay and microcephaly. The seizures were of different types, frequent and refractory to treatment, including different anticonvulsant drugs. Metabolic studies showed no significant changes. The initial electroencephalogram revealed bilateral paroxysmal activity with hemispherical diffusion. Brain MRI showed no pathological changes. Analysis of a whole exome sequencing (WES) based multigene panel for epilepsy disclosed a heterozygous CYFIP2 gene variant [c.258_266del; p.(Trp86_Ser88del)] established as de novo. We describe the case of an infant with EIEE due to a de novo heterozygous in-frame deletion of three amino acids in CYFIP2: c.258_266del; p.(Trp86_Ser88del). This in-frame deletion eliminates codon 87, a mutational hotspot associated with a particularly severe EIEE phenotype. All previous reports had missense variants with a presumably gain-of-function mechanism. The clinical picture of our patient is very similar to the ones with deleterious variants affecting codon 87 reported in the literature. Our case report is the first to describe a disease-causing in-frame deletion in CYFIP2 and reiterates a consistent genotype-phenotype correlation.	pt_PT
dc.description.version	info:eu-repo/semantics/publishedVersion	pt_PT
dc.identifier.citation	Da Silva Cardoso J, Gomes R, Abreu M, Parente Freixo J, Falcão Reis C, Garrido C. Clinical Role of Codon 87 of the CYFIP2 Gene in Early Infantile Epileptic Encephalopathy: A Clinical Case Description. Cureus. 2023;15(2):e35323. doi:10.7759/cureus.35323	pt_PT
dc.identifier.doi	10.7759/cureus.35323	pt_PT
dc.identifier.issn	2168-8184
dc.identifier.uri	http://hdl.handle.net/10400.16/2942
dc.language.iso	eng	pt_PT
dc.peerreviewed	yes	pt_PT
dc.publisher	Cureus, Inc.	pt_PT
dc.relation.publisherversion	https://www.cureus.com/articles/133380-clinical-role-of-codon-87-of-the-cyfip2-gene-in-early-infantile-epileptic-encephalopathy-a-clinical-case-description#!/	pt_PT
dc.rights.uri	http://creativecommons.org/licenses/by/4.0/	pt_PT
dc.subject	codon 87	pt_PT
dc.subject	cyfip2 gene	pt_PT
dc.subject	early infantile epileptic encephalopathy	pt_PT
dc.subject	infant	pt_PT
dc.subject	next-generation sequencing (ngs)	pt_PT
dc.title	Clinical Role of Codon 87 of the CYFIP2 Gene in Early Infantile Epileptic Encephalopathy: A Clinical Case Description	pt_PT
dc.type	journal article
dspace.entity.type	Publication
oaire.citation.conferencePlace	United States of America	pt_PT
oaire.citation.issue	2	pt_PT
oaire.citation.startPage	e35323	pt_PT
oaire.citation.title	Cureus	pt_PT
oaire.citation.volume	15	pt_PT
person.familyName	Parente Freixo
person.familyName	Garrido
person.givenName	João Nuno
person.givenName	Cristina
person.identifier.ciencia-id	7718-B310-7B26
person.identifier.orcid	0000-0002-8358-6267
person.identifier.orcid	0000-0001-5033-3522
rcaap.rights	openAccess	pt_PT
rcaap.type	article	pt_PT
relation.isAuthorOfPublication	c4b36336-471b-460b-a5cd-e71743f50fb7
relation.isAuthorOfPublication	50f6a7d9-e7f4-4d87-beae-67ff263cbe8d
relation.isAuthorOfPublication.latestForDiscovery	c4b36336-471b-460b-a5cd-e71743f50fb7