Exp Mol Med.  2008 Jun;40(3):271-275. 10.3858/emm.2008.40.3.271.

Predisposition of genetic disease by modestly decreased expression of GCH1 mutant allele

• Kim YS
• Choi YB
• Lee JH
• Yang SH
• Cho JH
• Shin CH
• Lee SD
• Paik MK
• Hong KM

• KMID: 756328
• DOI: http://doi.org/10.3858/emm.2008.40.3.271

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.

Keyword

dystonic disorders; germ-line mutation; point mutation; polymorphism; single nucleotide

MeSH Terms

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