Predisposition of genetic disease by modestly decreased expression of GCH1 mutant allele.
10.3858/emm.2008.40.3.271
- Author:
Yo Sik KIM
1
;
Yong Bock CHOI
;
Jeong Hwa LEE
;
Sei Hoon YANG
;
Ji Hyun CHO
;
Chang Ho SHIN
;
Sang Do LEE
;
Moon Kee PAIK
;
Kyeong Man HONG
Author Information
1. Research Institute, National Cancer Center, Goyang 410-769, Korea. kmhong@ncc.re.kr
- Publication Type:Case Reports ; Research Support, Non-U.S. Gov't
- Keywords:
dystonic disorders;
germ-line mutation;
point mutation;
polymorphism;
single nucleotide
- MeSH:
Child;
Clubfoot/genetics;
Dopamine/deficiency;
Dystonic Disorders/drug therapy/enzymology/*genetics/physiopathology;
GTP Cyclohydrolase/*genetics/metabolism;
Genes, Recessive;
*Genetic Predisposition to Disease;
Humans;
Levodopa/administration & dosage;
Male;
Mutation, Missense;
Pedigree;
Polymorphism, Genetic
- From:Experimental & Molecular Medicine
2008;40(3):271-275
- CountryRepublic of Korea
- Language:English
-
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.
