title: Identification and functional analysis of cystathionine beta-synthase gene mutations in patients with homocystinuria.
abstract: Homocystinuria is an autosomal recessive inborn error of metabolism that is most often caused by mutation in the cystathionine beta-synthase (CBS) gene. Patients may develop serious clinical manifestations such as lens dislocation, mental retardation, osteoporosis, and atherothrombotic vascular disease. Over 100 mutations have been reported, but so far, none have been reported in Korea. Mutation analysis of the CBS gene in six Korean patients with homocystinuria was performed by direct sequencing. Eight mutations were identified, including four known mutations (T257M, R336C, T353M, and G347S) and four novel mutations (L154Q, A155V, del234D, and A288T). All patients were compound heterozygotes. To characterize these mutations, normal or mutated forms of CBS were cloned into pcDNA3.1 expression vector followed by transfection into mammalian cells for transient expression. Whereas the expression levels of mutant proteins were comparable to that of normal control, enzyme activities of all the mutant forms were significantly decreased. In addition, a novel single nucleotide polymorphism, R18C, was identified, which showed one-third to two-thirds the enzyme activity of wild type and 1% of the allele frequency in normal control. The spectrum of mutations observed in Korean patients bears less resemblance to those observed in Western countries.
authors.affiliation: Division of Genetic Disease, Department of Biomedical Sciences, National Institute of Health, Seoul, South Korea.
authors.forename: Sook-Jin
authors.initials: SJ
authors.lastname: Lee
authors.forename: Dong Hwan
authors.initials: DH
authors.lastname: Lee
authors.forename: Han-Wook
authors.initials: HW
authors.lastname: Yoo
authors.forename: Soo Kyung
authors.initials: SK
authors.lastname: Koo
authors.forename: Eun-Sook
authors.initials: ES
authors.lastname: Park
authors.forename: Joo-Won
authors.initials: JW
authors.lastname: Park
authors.forename: Hun Gil
authors.initials: HG
authors.lastname: Lim
authors.forename: Sung-Chul
authors.initials: SC
authors.lastname: Jung
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D003541:Cystathionine beta-Synthase / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D005838:Genotype; D006712:Homocystinuria / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D007723:Korea / Q000453:epidemiology; D051379:Mice; D041681:NIH 3T3 Cells; D010641:Phenotype
chemical_list: D003541:Cystathionine beta-Synthase