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

PloS One
Berta Luzón-ToroS Borrego

Abstract

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 ...Continue Reading

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Citations

Sep 17, 2015·Journal of Investigative Surgery : the Official Journal of the Academy of Surgical Research·Akhmad MakhmudiGunadi
Jun 8, 2015·Journal of Pediatric Gastroenterology and Nutrition·Jin Sol LeeHyoung Doo Shin
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Methods Mentioned

BETA
genotyping
PCR
transfection

Software Mentioned

Polyphen
SeqScape®
SIFT
Quantity One
Ensembl

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