title: The molecular basis of UDP-galactose-4-epimerase (GALE) deficiency galactosemia in Korean patients.
abstract: OBJECTIVE
  UDP-galactose-4-epimerase (GALE) deficiency galactosemia is an autosomal recessive disorder and the prevalence of the disease varies among ethnic groups. We aimed to investigate molecular characteristics of the Korean patients with attenuated GALE activity and elevated galactose-1-phosphate levels in blood.
  
  
  METHODS
  In order to characterize the molecular defects underlying GALE deficiency, the GALE gene of 7 patients showing severe activity decreases was sequenced. PCR-RFLP was performed to confirm the presence of the mutations identified by sequencing.
  
  
  RESULTS
  Nine mutations were identified: 8 missense mutations (p.A25V, p.R40C, p.D69E, p.E165K, p.R169W, p.R239W, p.G302D, and p.R335H) and one nonsense mutation (p.W336X). Except for p.R335H, all of these mutations are novel. Six patients were compound heterozygotes (p.D69E/p.G302D, p.R40C/p.R169W, p.D69E/p.E165K, p.R239W/p.R335H, p.A25V/p.R169W, and p.G302D/p.R335H) and the remaining patient had only one mutation (p.W336X/not detected). Thirty patients with moderately reduced GALE activity were also tested by PCR-RFLP for the presence of the above mutation, and mutations were detected in 17 of these 30 patients. The frequency of p.G302D (9/30), p.R239W (6/30) and p.R169W (5/30) in our Korean patients with GALE deficiency galactosemia was relatively high.
  
  
  CONCLUSIONS
  We detected 9 mutations of the GALE gene in Korean galactosemia patients, and confirmed allelic heterogeneity in this disease.
authors.affiliation: Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Hyung-Doo
authors.initials: HD
authors.lastname: Park
authors.forename: Kyung Un
authors.initials: KU
authors.lastname: Park
authors.forename: Jin Q
authors.initials: JQ
authors.lastname: Kim
authors.forename: Choong Ho
authors.initials: CH
authors.lastname: Shin
authors.forename: Sei Won
authors.initials: SW
authors.lastname: Yang
authors.forename: Dong Hwan
authors.initials: DH
authors.lastname: Lee
authors.forename: Young-Han
authors.initials: YH
authors.lastname: Song
authors.forename: Junghan
authors.initials: J
authors.lastname: Song
mesh_terms: D004252:DNA Mutational Analysis; D017931:DNA Primers; D004262:DNA Restriction Enzymes; D005693:Galactosemias / Q000235:genetics*; D005808:Genes, Recessive / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007723:Korea; D009154:Mutation / Q000235:genetics*; D010744:Phosphoric Monoester Hydrolases / Q000097:blood; D012150:Polymorphism, Restriction Fragment Length; D017422:Sequence Analysis, DNA; D014534:UDPglucose 4-Epimerase / Q000235:genetics*
chemical_list: D017931:DNA Primers; D004262:DNA Restriction Enzymes; C069910:galactose-1-phosphatase; D010744:Phosphoric Monoester Hydrolases; D014534:UDPglucose 4-Epimerase