title: Molecular and biochemical characterization of the GALK1 gene in Korean patients with galactokinase deficiency.
abstract: Galactokinase (GALK) deficiency is an autosomal recessive disorder characterized by elevation of blood galactose concentration and diminished galactose-1-phosphate, leading to the production of galactitol. To investigate the molecular defects of GALK1 gene and the biochemical characteristics of their mutant proteins, PCR-direct sequencing and in vitro expression analysis in Cos7 cells were performed in five Korean patients with GALK deficiency galactosemia. Four missense mutations (p.G137R, p.R256W, p.R277Q, and p.V281M) and one small insertion (c.850_851insG) were identified. Among four patients with severely reduced GALK activity, two were found to be homozygotes for p.R256W and the other two were compound heterozygotes for different molecular defects (p.G137R/p.R277Q and p.V281M/c.850_851insG). One Patient with moderately decreased GALK activity was heterozygous for p.R256W. Expression analysis in Cos7 cells confirmed that each of the mutations resulted in reduction of GALK activity and caused GALK deficiency.
authors.affiliation: Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hyung-Doo
authors.initials: HD
authors.lastname: Park
authors.forename: You-Lim
authors.initials: YL
authors.lastname: Bang
authors.forename: Kyoung Un
authors.initials: KU
authors.lastname: Park
authors.forename: Jin Q
authors.initials: JQ
authors.lastname: Kim
authors.forename: Byung-Hoon
authors.initials: BH
authors.lastname: Jeong
authors.forename: Yong-Sun
authors.initials: YS
authors.lastname: Kim
authors.forename: Young-Han
authors.initials: YH
authors.lastname: Song
authors.forename: Junghan
authors.initials: J
authors.lastname: Song
mesh_terms: D000483:Alleles; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D005686:Galactokinase / Q000172:deficiency / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007231:Infant, Newborn; D007723:Korea; D016254:Mutagenesis, Insertional; D020125:Mutation, Missense
chemical_list: C484715:GALK1 protein, human; D005686:Galactokinase