title: The AGT gene in Africa: a distinctive minor allele haplotype, a polymorphism (V326I), and a novel PH1 mutation (A112D) in Black Africans.
abstract: We describe a novel missense mutation (A112D) and polymorphism (V326I) in the human AGT gene in two black African 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). V326I was found in DNA from normal control Blacks with an allele frequency of 3%. Expression studies confirmed that A112D reduced AGT enzyme activity by 95% while V326I had no effect. Both A112D and V326I were homozygous in both patients and lie on a variant of the minor allele of the AGT gene. This variant haplotype, Mi(A), includes an intron 1 duplication and intron 4 VNTR (38 repeat) but lacks the P11L and I340M normally associated with the minor allele in Caucasians. Among the South African Blacks tested, the Mi(A) haplotype had an allele frequency of 12% compared to 3 % for the Caucasian-type minor allele haplotype.
authors.affiliation: Department of Pediatrics, University of British Columbia, Vancouver BC, Canada. marioncm@interchange.ubc.ca
authors.forename: Marion B
authors.initials: MB
authors.lastname: Coulter-Mackie
authors.forename: Andrew
authors.initials: A
authors.lastname: Tung
authors.forename: Howard E
authors.initials: HE
authors.lastname: Henderson
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Toone
authors.forename: Derek A
authors.initials: DA
authors.lastname: Applegarth
mesh_terms: D000483:Alleles; D001483:Base Sequence; D044383:Black People / Q000235:genetics*; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D004591:Electrophoresis, Polyacrylamide Gel; D004926:Escherichia coli / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D005787:Gene Frequency; D005820:Genetic Testing; D006239:Haplotypes; D006801:Humans; D006960:Hyperoxaluria, Primary / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D011110:Polymorphism, Genetic; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013019:South Africa; D000637:Transaminases / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism
chemical_list: D011994:Recombinant Proteins; D004247:DNA; D000637:Transaminases; C019635:Alanine-glyoxylate transaminase