Background: The mucopolysaccharidosis type I (MPSI) is a lysosomal storage disease caused by a deficiency of alpha-L-iduronidase (IDUA) leading to the accumulation of partially degraded dermatan sulfate and heparan sulfate.
This 8-years this retrospective study analyzed data from42 MPSI patients.
The aim of this report was to investigate the possible origin of the p.P533R mutation in the Maghrebin population by constructing a single-nucleotide polymorphism (SNP) haplotype around the IDUA gene in order to propose a molecular proof of a founder effect of the MPSI allele.
Patients and Methods: All of the evaluated patients were Morocco (21 patients) and Tunisia (21 patients) with first cousins being the most frequent union. The diagnosis of MPSI patients often involves the combination of urine screening methods, enzyme analysis and DNA molecular analysis. In our study, we performed both sequencing and tetra-primer ARMS PCR assay to identify the common p.P533R mutation. Additionally, Haploview was used to determine the specific haplotype that cosegregates with the p.P533R mutation. Controls were genotyped to ensure that all the SNPs were in Hardy–Weinberg equilibrium.
Results: In the present report we confirmed the very strong impact of consanguinity on the expression of MPSI disease. Families of mixed ancestry shared seven common SNP haplotypes, which were observed in Moroccan and Tunisian families, thus indicating that a founder effect was present in the North African population.
Conclusion: The p.P533R missense mutation was identified in each MPSI patient originated from Morocco and Tunisia. Furthermore; the two populations exhibited the same IDUA haplotypes. These results suggest that the common haplotype may extend beyond the North African mixed ancestry population.