Variant "GDNF:c.-613C"
Search result: 1 record
Variant information
Gene:
GDNF 
Variant:
GDNF:c.-613C 
dbSNP ID:
no data 
GWAS trait:
no data 
Modifier statisitcs
Record:
1 
Disorder:
1 
Reference:
1 
Effect type:
Expressivity(1)  
Modifier effect:
Altered severity(1)  
Detail：
  • Target disease:
    Aganglionic Megacolon (HP:0002251)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered severity 
    Evidence:
    Assessment of genotype–phenotype associations 
    Effect:
    The Gdnf gene may modify the severity of HSCR in rats carrying Ednrb(sl) mutations.
    Reference:
    PMID26318480
    Title:
    Genetic variation in the GDNF promoter affects its expression and modifies the severity of Hirschsprung's disease (HSCR) in rats carrying Ednrb(sl) mutations.
    Species studied:
    Human
    Abstract:
    Glial cell line-derived neurotrophic factor (GDNF) is necessary for the migration of neural crest stem cells in the gut. However, mutations in GDNF per se are deemed neither necessary nor sufficient to cause Hirschsprung's disease (HSCR). In a previous study, a modifier locus on chromosome 2 in rats carrying Ednrb(sl) mutations was identified, and several mutations in the putative regulatory region of the Gdnf gene in AGH-Ednrb(sl) rats were detected. Specifically, the mutation -232C>T has been shown to be strongly associated with the severity of HSCR. In the present study, the influence of genetic variations on the transcription of the Gdnf gene was tested using dual-luciferase assay. Results showed that the mutation -613C>T, located near the mutation -232C>T in AGH-Ednrb(sl) rats, decreased Gdnf transcription in an in vitro dual-luciferase expression assay. These data suggested an important role of -613C in Gdnf transcription. Expression levels of the Gdnf gene may modify the severity of HSCR in rats carrying Ednrb(sl) mutations.