Background: Primary hyperoxaluria type 1 (PH1) is an autosomal recessive inherited metabolic disease, characterized by progressive kidney failure due to renal deposition of calcium oxalate. Mutations in the AGXT gene, encoding the liver-specific enzyme alanine glyoxylate aminotransferase, are responsible for the disease. We aimed to determine the mutational spectrum causing PH1 and to provide an accurate tool for diagnosis as well as for prenatal diagnosis in the affected families.
Methods: Direct sequencing was used to detect mutations in the AGXT gene in DNA samples from 13 patients belonging to 12 Tunisian families.
Results: Molecular analysis revealed five mutations causing PH1 in Tunisia. The mutations were identified along exons 1, 2, 4, 5 and 7. The most predominant mutations were the Maghrebian "p.I244T" and the Arabic "p.G190R". Furthermore, three other mutations characteristic of different ethnic groups were found in our study population. These results confirm the mutational heterogeneity related to PH1 in Tunisian population. All the mutations are in a homozygous state, reflecting the high impact of endogamy in our population.
Conclusion: Mutation analysis through DNA sequencing can provide a useful first line investigation for PH1. This identification could provide an accurate tool for prenatal diagnosis, genetic counseling and screen for potential presymptomatic individuals.
Keywords: AGT; AGT-Mi; CaOx; Decisional tree; Diagnosis; ESRD; HGMD; Historical event; Human Gene Mutation Database; NC; Nephrocalcinosis; PH1; Primary hyperoxaluria; Primary hyperoxaluria type 1; SNPs; alanine glyoxylate aminotransferase; calcium oxalate; end-stage renal disease; minor allele haplotype; nephrocalcinosis; pyridoxine; single nucleotide polymorphisms; vitamin B6.
© 2013 Elsevier B.V. All rights reserved.