title: A double mutation in AGXT gene in families with primary hyperoxaluria type 1.
abstract: Primary hyperoxaluria type 1 (PH1) is a severe autosomal recessive inherited disorder of glyoxylate metabolism caused by mutations in the AGXT gene on chromosome 2q37.3 that encodes the hepatic peroxisomal enzyme alanine:glyoxylate aminotransferase. These mutations are found throughout the entire gene and cause a wide spectrum of clinical severity. Rare in Europe, PH1 is responsible for 13% of the end stage renal failure in the Tunisian child. In the present work, we identified the double mutation c.32C>T (Pro11Leu) and c.731T>C (p.Ile244Thr) in AGXT gene in five unrelated Tunisian families with PH1 disease. Our results provide evidence regarding the potential involvement of c.32C>T, originally described as common polymorphism, on the resulting phenotype. We also reported an extreme intrafamilial heterogeneity in clinical presentation of PH1. Despite the same genetic background, the outcome of the affected members differs widely. The significant phenotypic heterogeneity observed within a same family, with a same genotype, suggests the existence of relevant modifier factors.
authors.affiliation: Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax, Université de Sfax, Tunisia. Electronic address: houda.kanoun@gmail.com.
authors.forename: Houda
authors.initials: H
authors.lastname: Kanoun
authors.forename: Faiçal
authors.initials: F
authors.lastname: Jarraya
authors.forename: Ikhlass
authors.initials: I
authors.lastname: Hadj Salem
authors.forename: Hichem
authors.initials: H
authors.lastname: Mahfoudh
authors.forename: Yosr
authors.initials: Y
authors.lastname: Chaabouni
authors.forename: Fatma
authors.initials: F
authors.lastname: Makni
authors.forename: Jamil
authors.initials: J
authors.lastname: Hachicha
authors.forename: Faiza
authors.initials: F
authors.lastname: Fakhfakh
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D003241:Consanguinity; D005260:Female; D006801:Humans; D006960:Hyperoxaluria, Primary / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000502:physiology; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D000637:Transaminases / Q000235:genetics*; D014416:Tunisia; D055815:Young Adult
chemical_list: D000637:Transaminases; C019635:Alanine-glyoxylate transaminase
keywords: AGT; AGXT gene mutation; CaOx; ESRD; Intrafamilial heterogeneity; PCR; PH1; Primary hyperoxaluria type 1; alanine:glyoxylate aminotransferase; calcium oxalate; end-stage renal disease; polymerase chain reaction; primary hyperoxaluria type 1; rmsd; root mean square deviation