Clinical Phenotpes Associated to Engrailed 2 Gene Alterations in a Series of Neuropediatric Patients

The engrailed homeobox protein (EN) plays an important role in the regionalization of the neural tube. EN distribution regulates the cerebellum and midbrain morphogenesis, as well as retinotectal synaptogenesis. In humans, the EN1 and EN2 genes code for the EN family of transcription factors. Geneti...

ver descrição completa

Detalhes bibliográficos
Autores: Carratalá-Marco, Francisco, Andreo-Lillo, Patricia, Martinez Morga, Marta, Escámez-Martínez, Teresa, Botella-López, Arancha, Bueno, Carlos, Martínez, Salvador
Formato: artículo
Fecha de publicación:2018
País:España
Recursos:Universidad Miguel Hernández de Elche
Repositorio:REDIUMH. Depósito Digital de la UMH
OAI Identifier:oai:dspace.umh.es:11000/35162
Acesso em linha:https://hdl.handle.net/11000/35162
Access Level:acceso abierto
Palavra-chave:EN2
behavioral disorders
cerebral palsy
encephalic structural anomalies
engrailed 2
epilepsy
genotype-genotype correlation
mental retardation
id ES_2c4ce2b49956e7dcde60802cf26cb59c
oai_identifier_str oai:dspace.umh.es:11000/35162
network_acronym_str ES
network_name_str España
repository_id_str
spelling Clinical Phenotpes Associated to Engrailed 2 Gene Alterations in a Series of Neuropediatric PatientsCarratalá-Marco, FranciscoAndreo-Lillo, PatriciaMartinez Morga, MartaEscámez-Martínez, TeresaBotella-López, AranchaBueno, CarlosMartínez, SalvadorEN2behavioral disorderscerebral palsyencephalic structural anomaliesengrailed 2epilepsygenotype-genotype correlationmental retardationThe engrailed homeobox protein (EN) plays an important role in the regionalization of the neural tube. EN distribution regulates the cerebellum and midbrain morphogenesis, as well as retinotectal synaptogenesis. In humans, the EN1 and EN2 genes code for the EN family of transcription factors. Genetic alterations in the expression of EN2 have been related to different neurologic conditions and more particularly to autism spectrum disorders (ASD). We aimed to study and compare the phenotypes of three series of patients: (1) patients with encephalic structural anomalies (ESA) and abnormalities in the genomic (DNA) and/or transcriptomic (RNAm) of EN2 (EN2-g), (2) ESA patients having other gene mutations (OG-g), and (3) ESA patients free of these mutations (NM-g). Subjects and Methods: We have performed a descriptive study on 109 patients who suffer from mental retardation (MR), cerebral palsy (CP), epilepsy (EP), and behavioral disorders (BD), showing also ESA in their encephalic MRI. We studied genomic DNA and transcriptional analysis (cDNA) on EN2 gene (EN2), and in other genes (OG): LIS1, PTAFR, PAFAH1B2, PAFAH1B3, FGF8, PAX2, D17S379, D17S1866, and SMG6 (D17S5), as a routine genetic diagnosis in ESA patients. Results: From 109 patients, fifteen meet the exclusion criteria. From the remaining 94 patients, 12 (12.8%) showed mutations in EN2 (EN2-g), 20 showed mutations in other studied genes (OG-g), and 62 did not showed any mutation (NM-g). All EN2-g patients, suffered from MR, nine EP, seven BD and four CP. The proportions of these phenotypes in EN2-g did not differ from those in the OG-g, but it was significantly higher when comparing EN2-g with NM-g (MR: p = 0.013; EP: p = 0.001; BD: p = 0.0001; CP: p = 0.07, ns). Groups EN2-g and OG-g showed a 100 and a 70% of comorbidity, respectively, being significantly (p = 0.04) greater than NM-group (62.9%). Conclusion: Our series reflects a significant effect of EN2 gene alterations in neurodevelopmental abnormalities associated to ESA. Conversely, although these EN2 related anomalies might represent a predisposition to develop brain diseases, our results did not support direct relationship between EN2 mutations and specific clinical phenotypes.FrontiersDepartamentos de la UMH::Farmacología, Pediatría y Química OrgánicaDepartamentos de la UMH::Histología y Anatomía202520252018info:eu-repo/semantics/articleapplication/pdf12application/pdfhttps://hdl.handle.net/11000/35162reponame:REDIUMH. Depósito Digital de la UMHinstname:Universidad Miguel Hernández de ElcheInglésdoi: 10.3389/fnana.2018.00061info:eu-repo/semantics/openAccessAttribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/oai:dspace.umh.es:11000/351622026-05-27T13:36:21Z
dc.title.none.fl_str_mv Clinical Phenotpes Associated to Engrailed 2 Gene Alterations in a Series of Neuropediatric Patients
title Clinical Phenotpes Associated to Engrailed 2 Gene Alterations in a Series of Neuropediatric Patients
spellingShingle Clinical Phenotpes Associated to Engrailed 2 Gene Alterations in a Series of Neuropediatric Patients
Carratalá-Marco, Francisco
EN2
behavioral disorders
cerebral palsy
encephalic structural anomalies
engrailed 2
epilepsy
genotype-genotype correlation
mental retardation
title_short Clinical Phenotpes Associated to Engrailed 2 Gene Alterations in a Series of Neuropediatric Patients
title_full Clinical Phenotpes Associated to Engrailed 2 Gene Alterations in a Series of Neuropediatric Patients
title_fullStr Clinical Phenotpes Associated to Engrailed 2 Gene Alterations in a Series of Neuropediatric Patients
title_full_unstemmed Clinical Phenotpes Associated to Engrailed 2 Gene Alterations in a Series of Neuropediatric Patients
title_sort Clinical Phenotpes Associated to Engrailed 2 Gene Alterations in a Series of Neuropediatric Patients
dc.creator.none.fl_str_mv Carratalá-Marco, Francisco
Andreo-Lillo, Patricia
Martinez Morga, Marta
Escámez-Martínez, Teresa
Botella-López, Arancha
Bueno, Carlos
Martínez, Salvador
author Carratalá-Marco, Francisco
author_facet Carratalá-Marco, Francisco
Andreo-Lillo, Patricia
Martinez Morga, Marta
Escámez-Martínez, Teresa
Botella-López, Arancha
Bueno, Carlos
Martínez, Salvador
author_role author
author2 Andreo-Lillo, Patricia
Martinez Morga, Marta
Escámez-Martínez, Teresa
Botella-López, Arancha
Bueno, Carlos
Martínez, Salvador
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Departamentos de la UMH::Farmacología, Pediatría y Química Orgánica
Departamentos de la UMH::Histología y Anatomía
dc.subject.none.fl_str_mv EN2
behavioral disorders
cerebral palsy
encephalic structural anomalies
engrailed 2
epilepsy
genotype-genotype correlation
mental retardation
topic EN2
behavioral disorders
cerebral palsy
encephalic structural anomalies
engrailed 2
epilepsy
genotype-genotype correlation
mental retardation
description The engrailed homeobox protein (EN) plays an important role in the regionalization of the neural tube. EN distribution regulates the cerebellum and midbrain morphogenesis, as well as retinotectal synaptogenesis. In humans, the EN1 and EN2 genes code for the EN family of transcription factors. Genetic alterations in the expression of EN2 have been related to different neurologic conditions and more particularly to autism spectrum disorders (ASD). We aimed to study and compare the phenotypes of three series of patients: (1) patients with encephalic structural anomalies (ESA) and abnormalities in the genomic (DNA) and/or transcriptomic (RNAm) of EN2 (EN2-g), (2) ESA patients having other gene mutations (OG-g), and (3) ESA patients free of these mutations (NM-g). Subjects and Methods: We have performed a descriptive study on 109 patients who suffer from mental retardation (MR), cerebral palsy (CP), epilepsy (EP), and behavioral disorders (BD), showing also ESA in their encephalic MRI. We studied genomic DNA and transcriptional analysis (cDNA) on EN2 gene (EN2), and in other genes (OG): LIS1, PTAFR, PAFAH1B2, PAFAH1B3, FGF8, PAX2, D17S379, D17S1866, and SMG6 (D17S5), as a routine genetic diagnosis in ESA patients. Results: From 109 patients, fifteen meet the exclusion criteria. From the remaining 94 patients, 12 (12.8%) showed mutations in EN2 (EN2-g), 20 showed mutations in other studied genes (OG-g), and 62 did not showed any mutation (NM-g). All EN2-g patients, suffered from MR, nine EP, seven BD and four CP. The proportions of these phenotypes in EN2-g did not differ from those in the OG-g, but it was significantly higher when comparing EN2-g with NM-g (MR: p = 0.013; EP: p = 0.001; BD: p = 0.0001; CP: p = 0.07, ns). Groups EN2-g and OG-g showed a 100 and a 70% of comorbidity, respectively, being significantly (p = 0.04) greater than NM-group (62.9%). Conclusion: Our series reflects a significant effect of EN2 gene alterations in neurodevelopmental abnormalities associated to ESA. Conversely, although these EN2 related anomalies might represent a predisposition to develop brain diseases, our results did not support direct relationship between EN2 mutations and specific clinical phenotypes.
publishDate 2018
dc.date.none.fl_str_mv 2018
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/11000/35162
url https://hdl.handle.net/11000/35162
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv doi: 10.3389/fnana.2018.00061
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
rights_invalid_str_mv Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.format.none.fl_str_mv application/pdf
12
application/pdf
dc.publisher.none.fl_str_mv Frontiers
publisher.none.fl_str_mv Frontiers
dc.source.none.fl_str_mv reponame:REDIUMH. Depósito Digital de la UMH
instname:Universidad Miguel Hernández de Elche
instname_str Universidad Miguel Hernández de Elche
reponame_str REDIUMH. Depósito Digital de la UMH
collection REDIUMH. Depósito Digital de la UMH
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869405218189344768
score 15,812429

Registos relacionados