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KMID : 0620920080400030271
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Experimental & Molecular Medicine
2008 Volume.40 No. 3 p.271 ~ p.275
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Predisposition of genetic disease by modestly decreased expression of GCH1 mutant allele
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Kim Yo-Sik
Yang Sei-Hoon
Paik Moon-Kee
Choi Yong-Bock
Lee Jeong-Hwa
Cho Ji-Hyun
Shin Chang-Ho
Lee Sang-Do
Hong Kyeong-Man
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Abstract
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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.
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KEYWORD
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dystonic disorders, germ-line mutation, point mutation, polymorphism, single nucleotide
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