Mucopolysaccharidosis I: α-L-Iduronidase mutations in three Tunisian families
Purchase on Springer.com
$39.95 / €34.95 / £29.95*
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.
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.
- Antonarakis SE, Krawczak M, Cooper DN (2001) The nature and mechanisms of human gene mutation. In: Scriver CR, Beaudet AL, Valle D, eds; Childs B, Kinzler KW, Vogelstein B, assoc eds. The Metabolic and Molecular Bases of Inherited Disease, 8th edn. New York: McGraw-Hill, 343–378.
- Alif N, Hess K, Straczek J, et al (1999) Mucopolysaccharidosis type I: characterization of a common mutation that causes Hurler syndrome in Moroccan subjects. Ann Hum Genet 63: 9–16. CrossRef
- Beesley CE, Meaney CA, Greeland G, et al (2001) Mutational analysis of mucopolysaccharidosis type I families: frequency of known mutations, identification of 17 novel mutations and in vitro expression of missense mutations. Hum Genet 109: 503–505.
- Bunge S, Kleijer WJ, Steglich C, et al (1994) Mucopolysaccaridosis type I: identification of 8 novel mutations and frequency of the common α-L-iduronidase mutations (W402X and Q70X) among European patients. Hum Mol Genet 3: 861–866.
- Chaabouni M, Ben Slimen M, Boudawara M, et al (2001) Mucopolysaccharidoses in children. Experience of a general pediatric service about 11 cases. Tunis Med 79: 222–300.
- Cooper CN, Youssoufian, H (1988) The CpG dinucleotide and genetic disease. Hum Genet 78: 151–155.
- Gatti R, Di Natale P, Villani GR, et al (1997) Mutations among Italian mucopolysaccharidosis type I patients. J Inherit Metab Dis 20: 803–806. CrossRef
- Hopwood JJ, Muller V, Smithson A, Bagget N (1979) A fluorometric assay using 4-methylumbelliferyl-α-L-iduronide for the estimation of α-L-iduronidase activity and the detection of Hurler and Scheie syndromes. Clin Chim Acta 92: 257–265. CrossRef
- Kakkis ED (2002) Enzyme replacement therapy for the mucopolysaccharide storage disorders. Expert Opin Investig Drugs 11: 675–685. CrossRef
- Kakkis ED, Muenzer J, Tiller GE, Waber L, Belmont J, et al (2001) Enzyme-replacement therapy in mucopolysaccharidosis I. N Engl J Med 344: 182–188. CrossRef
- Laradi S, Monastiri K, Ferchichi S, et al (2001) Clinico-biologic and molecular study of mucopolysaccharidosis in Central and Southern Tunisia. Ann Biol Clin 59: 100–104.
- Matte U, Yogalingam G, Brooks DA, et al (2003) Identification and characterization of 13 new mutations in mucopolysaccharidosis type I patients. Mol Genet Metab 78: 37–43. CrossRef
- Moskowitz SM, Phuong TT, Neufeld EF (1993) A deletion/insertion mutation in the IDUA gene in a Libyan Jewish patient with Hurler syndrome (mucopolysaccharidosis IH). Hum Mutat 2:71–73.
- Nelson J (1997) Incidence of the mucopolysaccharidoses in Northern Ireland. Hum Genet 101: 355–358. CrossRef
- Neufeld EF, Muenzer J (2001) The mucopolysaccharidoses. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds; Childs B, Kinzler KW, Vogelstein B, assoc. eds. The Metabolic and Molecular Bases of Inherited Disease, 8th edn. New York: McGraw-Hill, 3421–3452.
- Riou S, El Younsi C, Chaabouni H (1989) Consanguinité dans la population du nord de la Tunisie. Tunis Med 67: 167–172.
- Scott HS, Anson DS, Orsborn AM, (1991) Human α-L-Iduronidase: cDNA isolation and expression. Proc Natl Acad Sci USA 88: 9695–9699.
- Scott HS, Guo XH, Hopwood JJ, Morris CP (1992a) Structure and sequence of the human α-L-Iduronidase gene. Genomics 13: 1311–1313. CrossRef
- Scott HS, Litjens T, Nelson PV, Brooks DA, Hopwood JJ, Morris CP (1992b) α-L-Iduronidase mutations (Q70X and P533R) associate with a severe Hurler phenotype. Hum Mutat 1: 333–339.
- Scott HS, Nelson PV, Litjens T, Hopwood JJ, Morris CP (1993) Multiple polymorphisms within the α-L-iduronidase gene (IDUA): implications for a role in modification of MPS-I disease phenotype. Hum Mol Genet 2: 1471–1473.
- Scott HS, Bunge S, Gal A, Clarke LA, Morris CP, Hopwood JJ (1995) Molecular genetics of mucopolysaccaridosis type I: diagnostic, clinical and biological implications. Hum Mutat 6: 288–302. CrossRef
- Staba SL, Escolar ML, Poe M, et al (2004) Cord-blood transplants from unrelated donors in patients with Hurler's syndrome. N Engl J Med 350: 1960–1969. CrossRef
- Whitley CB, Belani KG, Chang PN, et al (1993) Long-term outcome of Hurler syndrome following bone marrow transplantation. Am J Med Genet 46: 209–218. CrossRef
- Mucopolysaccharidosis I: α-L-Iduronidase mutations in three Tunisian families
Journal of Inherited Metabolic Disease
Volume 28, Issue 6 , pp 1019-1026
- Cover Date
- Print ISSN
- Online ISSN
- Kluwer Academic Publishers
- Additional Links
- Industry Sectors
- Author Affiliations
- 1. Mount Sinai School of Medicine, New York University, New York, USA
- 2. Faculty of Pharmacy, Monastir, Tunisia
- 3. F Hached Hospital, Sousse, Tunisia
- 4. H Chaker Hospital, Sfax, Tunisia
- 5. Department of Human Genetics, Mount Sinai School of Medicine, New York University, 5th Ave. at 100th Street, New York, NY, 10029, USA