title: Mucopolysaccharidosis I: Alpha-L-Iduronidase mutations in three Tunisian families.
abstract: Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disease resulting from the defective activity of the enzyme alpha-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.
authors.affiliation: Mount Sinai School of Medicine, New York University, New York, NY 10029, USA.
authors.forename: S
authors.initials: S
authors.lastname: Laradi
authors.forename: T
authors.initials: T
authors.lastname: Tukel
authors.forename: M
authors.initials: M
authors.lastname: Erazo
authors.forename: J
authors.initials: J
authors.lastname: Shabbeer
authors.forename: L
authors.initials: L
authors.lastname: Chkioua
authors.forename: S
authors.initials: S
authors.lastname: Khedhiri
authors.forename: S
authors.initials: S
authors.lastname: Ferchichi
authors.forename: M
authors.initials: M
authors.lastname: Chaabouni
authors.forename: A
authors.initials: A
authors.lastname: Miled
authors.forename: R J
authors.initials: RJ
authors.lastname: Desnick
mesh_terms: D000483:Alleles; D003241:Consanguinity; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000378:metabolism; D005091:Exons; D005192:Family Health; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007068:Iduronidase / Q000235:genetics*; D007438:Introns; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D008059:Mucopolysaccharidosis I / Q000175:diagnosis* / Q000235:genetics*; D009154:Mutation; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D014416:Tunisia
chemical_list: D018076:DNA, Complementary; D007068:Iduronidase