title: Molecular heterogeneity of classical and Duarte galactosemia: mutation analysis by denaturing gradient gel electrophoresis.
abstract: Classical galactosemia is caused by one common missense mutation (Q188R) and by several rare mutations in the galactose-1-phosphate uridyltransferase (GALT) gene. The most common variant of GALT, the Duarte variant, occurs as two types, Duarte-1 (D-1) and Duarte-2 (D-2), both of which carry the sequence change N314D. D-1 increases, whereas D-2 decreases GALT activity. To study the molecular genetics of classical and Duarte galactosemia, we analyzed the GALT mutations in 30 families with classical galactosemia, in 10 families with the D-2 variant and in 3 individuals carrying the D-1 allele by denaturing gradient gel electrophoresis (DGGE). DGGE detected 59 of the 60 classical galactosemia alleles. Q188R accounted for 60%, K285N accounted for 28% of these alleles. Eight novel candidate galactosemia mutations were found. On all D-2 alleles N314D occurred in cis with two intronic sequence changes, on the D-1 alleles in cis with a neutral mutation in exon 7. We conclude that the mutations causing galactosemia are highly heterogeneous and that K285N is a second common galactosemia mutation in our population.
authors.affiliation: Department of Pediatrics, University of Vienna, Austria.
authors.forename: S
authors.initials: S
authors.lastname: Greber-Platzer
authors.forename: P
authors.initials: P
authors.lastname: Guldberg
authors.forename: S
authors.initials: S
authors.lastname: Scheibenreiter
authors.forename: C
authors.initials: C
authors.lastname: Item
authors.forename: E
authors.initials: E
authors.lastname: Schuller
authors.forename: N
authors.initials: N
authors.lastname: Patel
authors.forename: W
authors.initials: W
authors.lastname: Strobl
mesh_terms: D000328:Adult; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D017931:DNA Primers; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005693:Galactosemias / Q000145:classification / Q000235:genetics*; D018740:Genetic Heterogeneity; D005838:Genotype; D006801:Humans; D008297:Male; D009691:Nucleic Acid Denaturation; D010375:Pedigree; D017422:Sequence Analysis, DNA; D005694:UTP-Hexose-1-Phosphate Uridylyltransferase / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism
chemical_list: D017931:DNA Primers; D005694:UTP-Hexose-1-Phosphate Uridylyltransferase