RT Journal Article
T1 Comprehensive analysis of NRG1 common and rare variants in Hirschsprung patients.
A1 Luzón-Toro, Berta
A1 Torroglosa, Ana
A1 Núñez-Torres, Rocío
A1 Enguix-Riego, María Valle
A1 Fernández, Raquel María
A1 de Agustín, Juan Carlos
A1 Antiñolo, Guillermo
A1 Borrego, Salud
K1 Enfermedad de Hirschsprung
K1 Neurregulina-1
K1 Sistema Nervioso Entérico
K1 Variación Genética
AB 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.
PB Public Library of Science
YR 2012
FD 2012-05-04
LK http://hdl.handle.net/10668/841
UL http://hdl.handle.net/10668/841
LA en
NO Luzón-Toro B, Torroglosa A, Núñez-Torres R, Enguix-Riego MV, Fernández RM, de Agustín JC, et al. Comprehensive analysis of NRG1 common and rare variants in Hirschsprung patients. PLoS ONE; 7(5):e36524
NO Journal Article; Research Support, Non-U.S. Gov't;
DS RISalud
RD Apr 5, 2025