Predisposition of genetic disease by modestly decreased expression of GCH1 mutant allele.
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.
Kim
Yo Sik
YS
Research Institute, National Cancer Center, Goyang 410-769, Korea.
Choi
Yong Bock
YB
Lee
Jeong Hwa
JH
Yang
Sei Hoon
SH
Cho
Ji Hyun
JH
Shin
Chang Ho
CH
Lee
Sang Do
SD
Paik
Moon Kee
MK
Hong
Kyeong Man
KM
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
D007980:Levodopa; D006136:GTP Cyclohydrolase; D004298:Dopamine