PURPOSE: We previously reported a deletion of the Galactose-1-Phosphate Uridyl Transferase (GALT) gene. This deletion can cause apparent homozygosity for variants located on the opposite allele, potentially resulting in a discrepancy between the biochemical phenotype and the apparent genotype in an individual. The purpose of this study was to determine the deletion breakpoints, allowing the development of a rapid and reliable molecular test for the mutation. METHODS: A Polymerase Chain Reaction walking strategy was used to map the 5' and 3' breakpoints. The junction fragment was amplified and sequenced to precisely characterize the deletion breakpoints. RESULTS: The deletion has a bipartite structure involving two large segments of the GALT gene, while retaining a short internal segment of the gene. Molecular characterization allowed the development of a deletion specific Polymerase Chain Reaction-based assay. In 25 individuals who had a biochemical carrier galactosemia phenotype, but tested negative for 8 common GALT gene variants, 3 carried this deletion. CONCLUSION: This deletion occurs at an appreciable frequency and should be considered when there is a discrepancy between the genotype and biochemical phenotype. Many of the individuals carrying the allele were of Ashkenazi Jewish ancestry suggesting that the deletion may be a common cause of galactosemia in that population.
PURPOSE: We previously reported a deletion of the Galactose-1-Phosphate Uridyl Transferase (GALT) gene. This deletion can cause apparent homozygosity for variants located on the opposite allele, potentially resulting in a discrepancy between the biochemical phenotype and the apparent genotype in an individual. The purpose of this study was to determine the deletion breakpoints, allowing the development of a rapid and reliable molecular test for the mutation. METHODS: A Polymerase Chain Reaction walking strategy was used to map the 5' and 3' breakpoints. The junction fragment was amplified and sequenced to precisely characterize the deletion breakpoints. RESULTS: The deletion has a bipartite structure involving two large segments of the GALT gene, while retaining a short internal segment of the gene. Molecular characterization allowed the development of a deletion specific Polymerase Chain Reaction-based assay. In 25 individuals who had a biochemical carrier galactosemia phenotype, but tested negative for 8 common GALT gene variants, 3 carried this deletion. CONCLUSION: This deletion occurs at an appreciable frequency and should be considered when there is a discrepancy between the genotype and biochemical phenotype. Many of the individuals carrying the allele were of Ashkenazi Jewish ancestry suggesting that the deletion may be a common cause of galactosemia in that population.
Authors: Thanh-Thanh Claire V Tran; Ying Liu; Michael E Zwick; Dhanya Ramachandran; David J Cutler; Xiaoping Huang; Gerard T Berry; Judith L Fridovich-Keil Journal: JIMD Rep Date: 2015-02-15
Authors: Jochen K Lennerz; Robert J Timmerman; Dorothy K Grange; Michael R DeBaun; Andrew P Feinberg; Barbara A Zehnbauer Journal: J Mol Diagn Date: 2010-07-08 Impact factor: 5.568