Please use this identifier to cite or link to this item: https://doi.org/10.1186/s12887-018-1265-x
Title: NRG1 variant effects in patients with Hirschsprung disease
Authors: Gunadi, Budi N.Y.P.
Sethi R. 
Fauzi A.R.
Kalim A.S.
Indrawan T.
Iskandar K.
Makhmudi A.
Adrianto I.
San L.P.LLrp01459 
Keywords: neu differentiation factor
transcription factor
neu differentiation factor
NRG1 protein, human
protein binding
transcription factor
adolescent
Article
case control study
child
controlled study
disease course
female
genetic analysis
genetic code
genetic identification
genetic polymorphism
genetic variability
Hirschsprung disease
histopathology
human
human tissue
Indonesian
infant
major clinical study
male
muscle tissue
NRG1 gene
pathogenesis
population research
promoter region
protein motif
smooth muscle
adult
Asian continental ancestry group
DNA sequence
genetic predisposition
genetic variation
genetics
Hirschsprung disease
Indonesia
polymerase chain reaction
Adult
Asian Continental Ancestry Group
Case-Control Studies
Female
Genetic Predisposition to Disease
Genetic Variation
Hirschsprung Disease
Humans
Indonesia
Male
Neuregulin-1
Polymerase Chain Reaction
Protein Binding
Sequence Analysis, DNA
Transcription Factors
Issue Date: 2018
Citation: Gunadi, Budi N.Y.P., Sethi R., Fauzi A.R., Kalim A.S., Indrawan T., Iskandar K., Makhmudi A., Adrianto I., San L.P.LLrp01459 (2018). NRG1 variant effects in patients with Hirschsprung disease. BMC Pediatrics 18 (1) : 292. ScholarBank@NUS Repository. https://doi.org/10.1186/s12887-018-1265-x
Abstract: Background: Hirschsprung disease (HSCR) is a heterogeneous genetic disorder characterized by absence of ganglion cells along the intestines resulting in functional bowel obstruction. Mutations in neuregulin 1 (NRG1) gene have been implicated in some cases of intestinal aganglionosis. This study aims to investigate the contribution of the NRG1 gene to HSCR development in an Indonesian population. Methods: We analyzed the entire coding region of the NRG1 gene in 54 histopathologically diagnosed HSCR patients. Results: All patients were sporadic non-syndromic HSCR with 53/54 (98%) short-segment and 1/54 (2%) long-segment patients. NRG1 gene analysis identified one rare variant, c.397G > C (p.V133 L), and three common variants, rs7834206, rs3735774, and rs75155858. The p.V133 L variant was predicted to reside within a region of high mammalian conservation, overlapping with the promoter and enhancer histone marks of relevant tissues such as digestive and smooth muscle tissues and potentially altering the AP-4_2, BDP1_disc3, Egr-1_known1, Egr-1_known4, HEN1_2 transcription factor binding motifs. This p.V133 L variant was absent in 92 non-HSCR controls. Furthermore, the rs7834206 polymorphism was associated with HSCR by case-control analysis (p = 0.037). Conclusions: This study is the first report of a NRG1 rare variant associated with HSCR patients of South-East Asian ancestry and provides further insights into the contribution of NRG1 in the molecular genetic pathogenesis of HSCR. © The Author(s).
Source Title: BMC Pediatrics
URI: https://scholarbank.nus.edu.sg/handle/10635/175408
ISSN: 1471-2431
DOI: 10.1186/s12887-018-1265-x
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