title: Novel GALT variations and mutation spectrum in the Korean population with decreased galactose-1-phosphate uridyltransferase activity.
abstract: BACKGROUND
  Classic galactosemia (OMIM #230400) is an autosomal recessive metabolic disorder caused by a deficiency of the galactose-1-phosphate uridyltransferase (GALT, EC2.7.7.12) protein due to mutations in the GALT gene. The aim of this study was to provide a comprehensive and updated mutation spectrum of GALT in a Korean population.
  
  
  METHODS
  Thirteen unrelated patients screened positive for galactosemia in a newborn screening program were included in this study. They showed a reduced GALT enzyme activity in red blood cells. Direct sequencing of the GALT gene and in silico analyses were done to evaluate the impact of novel variations upon GALT enzyme activity. We also reviewed previous reports for GALT mutations in Koreans.
  
  
  RESULTS
  We identified six novel likely pathogenic variations including three missense (p.Ala101Asp, p.Tyr165His, and p.Pro257Thr), one small deletion/insertion [c.826_827delinsAA (p.Ala276Asn)], one frameshift (p.Asn96Serfs*5), and one splicing (c.378-1G > C) likely pathogenic variations. The most frequent variation was the Duarte variant (c.940A > G, 35.3%), followed by c.507G > C (p.Gln169His, 9.6%), among 34 Korean patients. Other mutations were widely scattered. None of the eight common mutations used for targeted mutation analysis in Western countries including p.Gln188Arg, p.Ser135Leu, p.Lys285Asn, p.Leu195Pro, p.Tyr209Cys, p.Phe171Ser, c.253-2A > G, and a 5 kb deletion, had been found in Koreans until this study.
  
  
  CONCLUSIONS
  Considering the mutation spectrum in Koreans, direct sequence analysis of entire GALT exons is recommended for accurate diagnosis. The mutations responsible for GALT deficiency in the Korean population were clearly different from those of other populations.
authors.forename: Rihwa
authors.initials: R
authors.lastname: Choi
authors.forename: Kyoung Il
authors.initials: KI
authors.lastname: Jo
authors.forename: Dae-Hyun
authors.initials: DH
authors.lastname: Ko
authors.forename: Dong Hwan
authors.initials: DH
authors.lastname: Lee
authors.forename: Junghan
authors.initials: J
authors.lastname: Song
authors.forename: Dong-Kyu
authors.initials: DK
authors.lastname: Jin
authors.forename: Chang-Seok
authors.initials: CS
authors.lastname: Ki
authors.forename: Soo-Youn
authors.initials: SY
authors.lastname: Lee
authors.forename: Jong-Won
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 135-710, Republic of Korea. lywmd@schmc.ac.kr.
authors.forename: Yong-Wha
authors.initials: YW
authors.lastname: Lee
authors.forename: Hyung-Doo
authors.initials: HD
authors.lastname: Park
mesh_terms: D044466:Asian People / Q000235:genetics; D005091:Exons; D005260:Female; D016368:Frameshift Mutation; D005693:Galactosemias / Q000235:genetics*; D014644:Genetic Variation; D006801:Humans; D054643:INDEL Mutation; D007223:Infant; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D012326:RNA Splicing; D017422:Sequence Analysis, DNA; D005694:UTP-Hexose-1-Phosphate Uridylyltransferase / Q000235:genetics*
chemical_list: D005694:UTP-Hexose-1-Phosphate Uridylyltransferase