Comprehensive analysis of NRG1 common and rare variants in Hirschsprung patients.

Hirschsprung disease (HSCR, OMIM 142623) is a developmental disorder characterized by the absence of ganglion cells along variable lengths of the distal gastrointestinal tract, which results in tonic contraction of the aganglionic gut segment and functional intestinal obstruction. The RET proto-onco...

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Autores principales:	Berta Luzón-Toro, Ana Torroglosa, Rocío Núñez-Torres, María Valle Enguix-Riego, Raquel María Fernández, Juan Carlos de Agustín, Guillermo Antiñolo, Salud Borrego
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c478cb8d57554781a6f0e80ca5d2d016
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spelling	oai:doaj.org-article:c478cb8d57554781a6f0e80ca5d2d0162021-11-18T07:19:36ZComprehensive analysis of NRG1 common and rare variants in Hirschsprung patients.1932-620310.1371/journal.pone.0036524https://doaj.org/article/c478cb8d57554781a6f0e80ca5d2d0162012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22574178/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Hirschsprung disease (HSCR, OMIM 142623) is a developmental disorder characterized by the absence of ganglion cells along variable lengths of the distal gastrointestinal tract, which results in tonic contraction of the aganglionic gut segment and functional intestinal obstruction. The RET proto-oncogene is the major gene for HSCR with differential contributions of its rare and common, coding and noncoding mutations to the multifactorial nature of this pathology. Many other genes have been described to be associated with the pathology, as NRG1 gene (8p12), encoding neuregulin 1, which is implicated in the development of the enteric nervous system (ENS), and seems to contribute by both common and rare variants. Here we present the results of a comprehensive analysis of the NRG1 gene in the context of the disease in a series of 207 Spanish HSCR patients, by both mutational screening of its coding sequence and evaluation of 3 common tag SNPs as low penetrance susceptibility factors, finding some potentially damaging variants which we have functionally characterized. All of them were found to be associated with a significant reduction of the normal NRG1 protein levels. The fact that those mutations analyzed alter NRG1 protein would suggest that they would be related with HSCR disease not only in Chinese but also in a Caucasian population, which reinforces the implication of NRG1 gene in this pathology.Berta Luzón-ToroAna TorroglosaRocío Núñez-TorresMaría Valle Enguix-RiegoRaquel María FernándezJuan Carlos de AgustínGuillermo AntiñoloSalud BorregoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 5, p e36524 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Berta Luzón-Toro Ana Torroglosa Rocío Núñez-Torres María Valle Enguix-Riego Raquel María Fernández Juan Carlos de Agustín Guillermo Antiñolo Salud Borrego Comprehensive analysis of NRG1 common and rare variants in Hirschsprung patients.
description	Hirschsprung disease (HSCR, OMIM 142623) is a developmental disorder characterized by the absence of ganglion cells along variable lengths of the distal gastrointestinal tract, which results in tonic contraction of the aganglionic gut segment and functional intestinal obstruction. The RET proto-oncogene is the major gene for HSCR with differential contributions of its rare and common, coding and noncoding mutations to the multifactorial nature of this pathology. Many other genes have been described to be associated with the pathology, as NRG1 gene (8p12), encoding neuregulin 1, which is implicated in the development of the enteric nervous system (ENS), and seems to contribute by both common and rare variants. Here we present the results of a comprehensive analysis of the NRG1 gene in the context of the disease in a series of 207 Spanish HSCR patients, by both mutational screening of its coding sequence and evaluation of 3 common tag SNPs as low penetrance susceptibility factors, finding some potentially damaging variants which we have functionally characterized. All of them were found to be associated with a significant reduction of the normal NRG1 protein levels. The fact that those mutations analyzed alter NRG1 protein would suggest that they would be related with HSCR disease not only in Chinese but also in a Caucasian population, which reinforces the implication of NRG1 gene in this pathology.
format	article
author	Berta Luzón-Toro Ana Torroglosa Rocío Núñez-Torres María Valle Enguix-Riego Raquel María Fernández Juan Carlos de Agustín Guillermo Antiñolo Salud Borrego
author_facet	Berta Luzón-Toro Ana Torroglosa Rocío Núñez-Torres María Valle Enguix-Riego Raquel María Fernández Juan Carlos de Agustín Guillermo Antiñolo Salud Borrego
author_sort	Berta Luzón-Toro
title	Comprehensive analysis of NRG1 common and rare variants in Hirschsprung patients.
title_short	Comprehensive analysis of NRG1 common and rare variants in Hirschsprung patients.
title_full	Comprehensive analysis of NRG1 common and rare variants in Hirschsprung patients.
title_fullStr	Comprehensive analysis of NRG1 common and rare variants in Hirschsprung patients.
title_full_unstemmed	Comprehensive analysis of NRG1 common and rare variants in Hirschsprung patients.
title_sort	comprehensive analysis of nrg1 common and rare variants in hirschsprung patients.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/c478cb8d57554781a6f0e80ca5d2d016
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Comprehensive analysis of NRG1 common and rare variants in Hirschsprung patients.

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