title: Three missense mutations in the galactose-1-phosphate uridyltransferase gene of three families with mild galactosaemia.
abstract: Classical galactosaemia caused by deficiency of galactose-1-phosphate uridyltransferase (GALT) is characterized by acute symptoms of hepatocellular dysfunction, sepsis, cataracts and failure to thrive. Galactose limitation reverses these complications immediately, however, most of these children have a long-term complication of verbal dyspraxia mental retardation and ovarian failure. The GALT gene was cloned and several mutations including the common Q188R have been reported. In this study the coding region of GALT was amplified by polymerase chain reaction from genomic DNA of classical galactosaemic individuals and characterized by direct sequencing of the products. Three missense mutations were identified in three patients with a mild galactosaemic variant: (1) replacement of threonine-138 by methionine (T138M); (2) replacement of arginine by tryptophan (R259W); and (3) replacement of threonine by alanine (T350A). All three galactosaemic individuals, one girl and two boys, have varying degrees of residual GALT activity in RBC and their galactose-1-phosphate levels decreased much faster than in other galactosaemic patients. These missense mutations occur in regions that are not highly conserved domains.
  
  
  CONCLUSIONS
  The study of the molecular basis related to the phenotype variation may indeed help to prognosticate the outcome of patients with classical galactosaemia.
authors: Universitäts-Kinderkrankenhaus, München, Germany.
authors: Y S
authors: YS
authors: Shin
authors: B S
authors: BS
authors: Gathof
authors: T
authors: T
authors: Podskarbi
authors: M
authors: M
authors: Sommer
authors: R
authors: R
authors: Giugliani
authors: U
authors: U
authors: Gresser
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D005260:Female; D005693:Galactosemias / Q000097:blood / Q000235:genetics*; D005695:Galactosephosphates / Q000097:blood; D005796:Genes; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D005694:UTP-Hexose-1-Phosphate Uridylyltransferase / Q000235:genetics*
chemical_list: D005695:Galactosephosphates; C029973:galactose-1-phosphate; D005694:UTP-Hexose-1-Phosphate Uridylyltransferase