title: Mutational Analysis of Agxt in Tunisian Population with Primary Hyperoxaluria Type 1.
abstract: BACKGROUND
  Primary hyperoxaluria type 1 (PH1) is an autosomal recessive metabolic disorder caused by inherited mutations in the AGXT gene encoding liver peroxisomal alanine:glyoxylate aminotransferase (AGT). PH1 is a clinically and genetically heterogeneous disorder. The aim of our study was to analyze and characterize the mutational spectrum of PH1 in Tunisian patients.
  
  
  METHODS
  Molecular studies of 146 Tunisian patients suspected with PH were performed by PCR/Restriction fragment length polymorphism (RFLP) to detect seven mutations described as the most common. Direct sequencing for the 11 exons was performed in patients in whom any mutation was not identified.
  
  
  RESULTS
  The genetic diagnosis of PH1 was confirmed in 62.3% of patients. The first molecular approach based on PCR/restriction enzyme test was positive in 37.6% of patients, whereas the second molecular approach based on whole gene sequencing was successful in 24% of cases. Twelve pathogenic mutations were detected in our cohort. Two mutations were novel, and five were detected for the first time in Tunisians. The three most frequent mutations were p.Ile244Thr, p.Gly190Arg, and c.33dupC, with a frequency of 43.4%, 21.4%, and 13.1%, respectively.
  
  
  CONCLUSIONS
  The two novel mutations detected in our study extend the spectrum of known AGXT gene mutations. The screen for the mutations identified in this study can provide a useful, cost-effective, and first-line investigation in Tunisian PH1 patients.
authors.affiliation: Biochemistry Department, Sahloul University Hospital, Sousse, Tunisia.
authors.forename: Saoussen
authors.initials: S
authors.lastname: M'dimegh
authors.affiliation: Biochemistry Department, Sahloul University Hospital, Sousse, Tunisia.
authors.forename: Asma
authors.initials: A
authors.lastname: Omezzine
authors.affiliation: Biochemistry Department, Sahloul University Hospital, Sousse, Tunisia.
authors.forename: Ibtihel
authors.initials: I
authors.lastname: M'barek
authors.affiliation: Biochemistry Department, Sahloul University Hospital, Sousse, Tunisia.
authors.forename: Amira
authors.initials: A
authors.lastname: Moussa
authors.affiliation: Biochemistry Department, Sahloul University Hospital, Sousse, Tunisia.
authors.forename: Sameh
authors.initials: S
authors.lastname: Mabrouk
authors.affiliation: Internal Medicine A Department, Charles Nicolle University Hospital, Tunis, Tunisia.
authors.forename: Hayet
authors.initials: H
authors.lastname: Kaarout
authors.affiliation: Laboratory of Inborn Metabolic Diseases, Centre de Biologie Est, Hospices Civils de Lyon, Lyon, France.
authors.forename: Geneviéve
authors.initials: G
authors.lastname: Souche
authors.affiliation: Pediatric Department, Sahloul University Hospital, Sousse, Tunisia.
authors.forename: Jalel
authors.initials: J
authors.lastname: Chemli
authors.affiliation: Nephrology Department, Fatouma Bourguiba University Hospital, Monastir, Tunisia.
authors.forename: Sabra
authors.initials: S
authors.lastname: Aloui
authors.affiliation: Laboratory of Inborn Metabolic Diseases, Centre de Biologie Est, Hospices Civils de Lyon, Lyon, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Aquaviva-Bourdain
authors.affiliation: Nephrology Department, Sahloul University Hospital, Sousse, Tunisia.
authors.forename: Abdellatif
authors.initials: A
authors.lastname: Achour
authors.affiliation: Pediatric Department, Sahloul University Hospital, Sousse, Tunisia.
authors.forename: Saoussen
authors.initials: S
authors.lastname: Abroug
authors.affiliation: Biochemistry Department, Sahloul University Hospital, Sousse, Tunisia.
authors.forename: Ali
authors.initials: A
authors.lastname: Bouslama
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D006239:Haplotypes; D006801:Humans; D006960:Hyperoxaluria, Primary / Q000235:genetics*; D007223:Infant; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D000637:Transaminases / Q000235:genetics*; D055815:Young Adult
chemical_list: D000637:Transaminases; C019635:Alanine-glyoxylate transaminase
keywords: AGXT; PH1; Primary hyperoxaluria; genotype-phenotype correlations