Predisposition of genetic disease by modestly decreased expression of GCH1 mutant allele
Experimental & Molecular Medicine
;
: 271-275, 2008.
Article
in English
| WPRIM
| ID: wpr-205430
ABSTRACT
Recently it was shown that single nucleotide polymorphisms (SNPs) can explain individual variation because of the small changes of the gene expression level and that the 50% decreased expression of an allele might even lead to predisposition to cancer. In this study, we found that a decreased expression of an allele might cause predisposition to genetic disease. Dopa responsive dystonia (DRD) is a dominant disease caused by mutations in GCH1 gene. The sequence analysis of the GCH1 in a patient with typical DRD symptoms revealed two novel missense mutations instead of a single dominant mutation. Family members with either of the mutations did not have any symptoms of DRD. The expression level of a R198W mutant allele decreased to about 50%, suggesting that modestly decreased expression caused by an SNP should lead to predisposition of a genetic disease in susceptible individuals.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pedigree
/
Polymorphism, Genetic
/
Clubfoot
/
Dopamine
/
Levodopa
/
Genetic Predisposition to Disease
/
Mutation, Missense
/
Dystonic Disorders
/
Genes, Recessive
/
GTP Cyclohydrolase
Limits:
Child
/
Humans
/
Male
Language:
English
Journal:
Experimental & Molecular Medicine
Year:
2008
Type:
Article
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