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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.

SUBMITTER: Kim YS

PROVIDER: S-EPMC2679294 | biostudies-literature | 2008 Jun

REPOSITORIES: biostudies-literature

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

Kim Yo Sik YS 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

Experimental & molecular medicine 20080601 3

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 w ...[more]

PMID: 18587264

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