title: Maternal isodisomy of the telomeric end of chromosome 2 is responsible for a case of primary hyperoxaluria type 1.
abstract: Primary hyperoxaluria type 1 (PH1) is an autosomal recessive disorder of glyoxylate metabolism, in which excessive oxalates are formed by the liver and excreted by the kidneys, causing a wide spectrum of disease, ranging from renal failure in infancy to mere renal stones in late adulthood. This disease is caused by a deficiency of alanine:glyoxylate aminotransferase (AGT), which is encoded by a single copy gene, AGXT, located in 2q37.3. We identified an apparently homozygous, loss-of-function, mutation in a patient; the gene defect was present in the heterozygous mother but not in the patient's father. We performed a microsatellite repeat analysis using 13 specific chromosome 2 markers and non-chromosome 2 minisatellites. Six specific chromosome 2 markers showed an apparently homozygous maternal inheritance while four showed a biparental transmission consistent with paternity (confirmed by minisatellite analysis). Quantitative PCR of AGXT exons 1 and 3 on the patient's and parents genomic DNA revealed the presence of two copies of the gene. This is the first case of PH1 caused by segmental maternal isodisomy of 2q37.3.
authors.affiliation: Biochimie Pédiatrique, Hôpital Debrousse, Lyon, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Chevalier-Porst
authors.forename: Marie-Odile
authors.initials: MO
authors.lastname: Rolland
authors.forename: Pierre
authors.initials: P
authors.lastname: Cochat
authors.forename: Dominique
authors.initials: D
authors.lastname: Bozon
mesh_terms: D000483:Alleles; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D016368:Frameshift Mutation; D006720:Homozygote; D006801:Humans; D006960:Hyperoxaluria, Primary / Q000201:enzymology / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats; D009035:Mothers; D016254:Mutagenesis, Insertional; D016615:Telomere / Q000235:genetics*; D000637:Transaminases / Q000235:genetics; D024182:Uniparental Disomy
chemical_list: D004247:DNA; D000637:Transaminases; C019635:Alanine-glyoxylate transaminase