title: The major allele of the alanine:glyoxylate aminotransferase gene: seven novel mutations causing primary hyperoxaluria type 1.
abstract: We describe 7 novel mutations occurring on the major allele of the human AGT gene in patients with primary hyperoxaluria type 1, an autosomal recessive disease resulting from a deficiency of the liver peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT; EC 2.6.1.44). These mutations include 3 small deletions, 570delG, 744delC, and 983_988del, two splice junction mutations, IVS7-1G-->C and IVS8+1G-->T, and two nonsense mutations, R111X and W251X. We have also identified recurrences of previously identified reported mutations, 679-(IVS6+2)delAAgt, IVS8-3C-->G and 33insC. Deletion mutation 679-(IVS6+2)delAAgt has now been identified in a second Chinese patient and may be specific to that population. In contrast, 33insC has been found in patients of varying ethnic and racial backgrounds; a single vs multiple origin for this mutation is thus an intriguing question. It also appears to occur at a high frequency on the major allele. Five of the novel mutations were detected in patients who were compound heterozygotes for one of the common mis-targeting mutation, G170R or F152I, while the other two mutations occurred in the same patient.
authors.affiliation: Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada V6H 3V4. marioncm@interchange.ubc.ca
authors.forename: Marion B
authors.initials: MB
authors.lastname: Coulter-Mackie
authors.forename: Derek
authors.initials: D
authors.lastname: Applegarth
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Toone
authors.forename: Howard
authors.initials: H
authors.lastname: Henderson
mesh_terms: D000328:Adult; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D006801:Humans; D006960:Hyperoxaluria, Primary / Q000235:genetics*; D007223:Infant; D008099:Liver / Q000201:enzymology; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013577:Syndrome; D000637:Transaminases / Q000235:genetics*
chemical_list: D000637:Transaminases; C019635:Alanine-glyoxylate transaminase