Mucopolysaccharidosis I: [alpha]-L-Iduronidase mutations in three Tunisian families

• Published in: Journal of inherited metabolic disease Vol. 28; no. 6; p. 1019
• Main Authors: Laradi, S, Tukel, T, Erazo, M, Shabbeer, J, Chkioua, L, Khedhiri, S, Ferchichi, S, Chaabouni, M, Miled, A, Desnick, R J
• Format: Journal Article
• Language: English
• Published: Dordrecht Blackwell Publishing Ltd 01-11-2005
• ISSN: 0141-8955; 1573-2665
• DOI: 10.1007/s10545-005-0197-4

Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disease resulting from the defective activity of the enzyme α-L-iduronidase (IDUA). The disease has severe and milder phenotypic subtypes. The IDUA mutations in five MPS I patients from three unrelated families from central and southern Tunisia were determined by amplifying and sequencing each of the IDUA exons and intron-exon junctions. Two novel IDUA mutations, c.1805delTinsGAACA in exon 13 and I270S in exon 7, and two previously reported mutations, P533R and R628X, were detected. The two patients in family 1 who had the Hurler phenotype were homoallelic for the novel deletion-insertion mutation. The patient in family 2 who also had the Hurler phenotype was heteroallelic for the novel missense mutation I270S and the previously reported nonsense mutation R628X. The two patients in family 3 who had the Hurler-Scheie phenotype were homoallelic for P533R. In addition, six known IDUA polymorphisms were identified. These are the first Tunisian MPS I patients to be genotyped. The identification of these mutations and their genotype-phenotype correlations should facilitate prenatal diagnosis and counselling for MPS I in Tunisia, where a very high rate of consanguinity exists.