title: Predisposition of genetic disease by modestly decreased expression of GCH1 mutant allele.
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.
authors.affiliation: Research Institute, National Cancer Center, Goyang 410-769, Korea.
authors.forename: Yo Sik
authors.initials: YS
authors.lastname: Kim
authors.forename: Yong Bock
authors.initials: YB
authors.lastname: Choi
authors.forename: Jeong Hwa
authors.initials: JH
authors.lastname: Lee
authors.forename: Sei Hoon
authors.initials: SH
authors.lastname: Yang
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Cho
authors.forename: Chang Ho
authors.initials: CH
authors.lastname: Shin
authors.forename: Sang Do
authors.initials: SD
authors.lastname: Lee
authors.forename: Moon Kee
authors.initials: MK
authors.lastname: Paik
authors.forename: Kyeong Man
authors.initials: KM
authors.lastname: Hong
mesh_terms: D002648:Child; D003025:Clubfoot / Q000235:genetics; D004298:Dopamine / Q000172:deficiency; D020821:Dystonic Disorders / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D006136:GTP Cyclohydrolase / Q000235:genetics* / Q000378:metabolism; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D011110:Polymorphism, Genetic
chemical_list: D007980:Levodopa; D006136:GTP Cyclohydrolase; D004298:Dopamine