Characterization of an unusual deletion of the galactose-1-phosphate uridyl transferase (GALT) gene.
OBJECTIVE
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.


CONCLUSIONS
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.
Coffee
Bradford
B
Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia 30033, USA.
Hjelm
Lawrence N
LN
DeLorenzo
Angela
A
Courtney
Ebony M
EM
Yu
Chunli
C
Muralidharan
Kasinathan
K
D001483:Base Sequence; D004247:DNA / Q000032:analysis; D053903:DNA Breaks, Double-Stranded; D004252:DNA Mutational Analysis; D005693:Galactosemias / Q000201:enzymology / Q000235:genetics*; D017353:Gene Deletion; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008969:Molecular Sequence Data; D010641:Phenotype; D016133:Polymerase Chain Reaction; D005694:UTP-Hexose-1-Phosphate Uridylyltransferase / Q000235:genetics*
D004247:DNA; D005694:UTP-Hexose-1-Phosphate Uridylyltransferase