title: A novel mutation in the AGXT gene causing primary hyperoxaluria type I: genotype-phenotype correlation.
abstract: Primary hyperoxaluria type I (PH1) is an autosomal recessive metabolic disorder caused by inherited mutations in the AGXT gene encoding liver peroxisomal alanine : glyoxylate aminotransferase (AGT) which is deficient or mistargeted to mitochondria. PH1 shows considerable phenotypic and genotypic heterogeneity. The incidence and severity of PH1 varies in different geographic regions. DNA samples of the affected members from two unrelated Tunisian families were tested by amplifying and sequencing each of the AGXT exons and intron-exon junctions. We identified a novel frameshift mutation in the AGXT gene, the c.406_410dupACTGC resulting in a truncated protein (p.Gln137Hisfs*19). It is found in homozygous state in two nonconsanguineous unrelated families from Tunisia. These molecular findings provide genotype/phenotype correlations in the intrafamilial phenotypic and permit accurate carrier detection, and prenatal diagnosis. The novel p.Gln137Hisfs*19 mutation detected in our study extend the spectrum of known AGXT gene mutations in Tunisia.
authors.affiliation: Biochemistry Department, LR12SP11, Sahloul University Hospital, 4054 Sousse, Tunisia.sawsen_mdimegh@live.fr.
authors.forename: Saoussen
authors.initials: S
authors.lastname: M'Dimegh
authors.forename: Cécile
authors.initials: C
authors.lastname: Aquaviva-Bourdain
authors.forename: Asma
authors.initials: A
authors.lastname: Omezzine
authors.forename: Ibtihel
authors.initials: I
authors.lastname: M'Barek
authors.forename: Geneviéve
authors.initials: G
authors.lastname: Souche
authors.forename: Dorsaf
authors.initials: D
authors.lastname: Zellama
authors.forename: Kamel
authors.initials: K
authors.lastname: Abidi
authors.forename: Abdelattif
authors.initials: A
authors.lastname: Achour
authors.forename: Tahar
authors.initials: T
authors.lastname: Gargah
authors.forename: Saoussen
authors.initials: S
authors.lastname: Abroug
authors.forename: Ali
authors.initials: A
authors.lastname: Bouslama
mesh_terms: D001483:Base Sequence; D002648:Child; D005091:Exons; D005260:Female; D016368:Frameshift Mutation; D015870:Gene Expression; D005808:Genes, Recessive; D056726:Genetic Association Studies; D055106:Genome-Wide Association Study; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D006960:Hyperoxaluria, Primary / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D007438:Introns; D008297:Male; D010375:Pedigree; D010641:Phenotype; D011110:Polymorphism, Genetic; D012720:Severity of Illness Index; D000637:Transaminases / Q000235:genetics*; D014416:Tunisia; D055815:Young Adult
chemical_list: D000637:Transaminases; C019635:Alanine-glyoxylate transaminase