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Open Access 01-12-2011 | Research

Molecular analysis of mucopolysaccharidosis type I in Tunisia: identification of novel mutation and eight Novel polymorphisms

Authors: Latifa Chkioua, Souhir Khedhiri, Asma Kassab, Amina Bibi, Salima Ferchichi, Roseline Froissart, Christine Vianey-Saban, Sandrine Laradi, Abdelhedi Miled

Published in: Diagnostic Pathology | Issue 1/2011

Abstract

Mucopolysaccharidosis type I (MPS I) is an autosomal recessive lysosomal storage disorder caused by a genetic defect in alpha-L-iduronidase (IDUA) which is involved in the degradation of dermatan and heparan sulfates. The disease has severe and milder phenotypic subtypes. The aim of this study was the detection of mutations in the IDUA gene from 12 additional MPS I patients with various clinical phenotypes (severe, 8 cases; intermediate, 3 cases; mild, 1 case).

Patients and methods

In this study, the IDUA mutations in eight unrelated Tunisian families were performed by amplifying and sequencing the IDUA exons and intron-exon jonctions.

Results

Five IDUA mutations were detected: one is the L578Q, a novel mutation found, in milder patient. The others were the previously described: P533R, Y581X, F602X and R628X that produce a severe and intermediate phenotype. In addition, eighteen variants, including eight previously unreported polymorphisms (IVS6+21c > a, IVS7+79c > t, IVS7-45 g > c, IVS9+36t > c, IVS10+140c > a, IVS11+33c > t, IVS12+13c > t and IVS12-31c > g), were detected.

Conclusion

This paper, showed a heterogeneous pattern of mutations and polymorphisms among Tunisian patients.

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Neufeld EF, Muenzer J: The mucopolysaccharidoses. The Metabolic and Molecular Bases of Inherited Disease. Edited by: Scriver CR, Beaudet AL, Sly WS, Valle D. 2001, New York: McGraw-Hill, 3421-3452.

Scott HS, Anson DS, Orsborn AM, Nelson PV, Clements PR, Morris CP, Hopwood JJ: Human alpha-L-iduronidase: cDNA isolation and expression. Proc Natl Acad Sci USA. 1991, 88: 9695-9699. 10.1073/pnas.88.21.9695.PubMedCentralCrossRefPubMed

Scott HS, Guo XH, Hopwood JJ, Morris CP: Structure and sequence of the human alpha-L-iduronidase gene. Genomics. 1992, 13: 1311-1313. 10.1016/0888-7543(92)90053-U.CrossRefPubMed

Chaabouni M, Ben Slimen M, Boudawara M, Ben Amar H, Mahfoudh A, Ayadi F, Ben Halima N, Hachicha M, Karaay A, Triki A: Mucopolysaccharidoses in children. Experience of a general pediatric service 11 cases. Tunis Med. 2001, 79: 222-300.PubMed

Haj Khelil A, Laradi S, Miled A, Tadmouri GO, Ben Chibani J, Perrin P: Clinical and molecular aspects of hemoglobinopathies in Tunisia. Clin Chim Acta. 2004, 340: 127-137. 10.1016/j.cccn.2003.10.022.CrossRefPubMed

Hartree EF: Determination of protein: a modification of the Lowry method that gives a linear photometric response. Anal Biochem. 1972, 48: 422-427. 10.1016/0003-2697(72)90094-2.CrossRefPubMed

Sambrook J, Fritisch EF, Maniatis T: Molecular cloning: a laboratory manual. 1989, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York

Nelson J: Incidence of the mucopolysaccharidoses in Northern Irland. Hum Genet. 1997, 101: 255-258. 10.1007/s004390050626.CrossRef

Ben Turkia H, Tebib N, Azzouz H, Abdelmoula MS, Ben Chehida A, Chemli J, Monastiri K, Chaabouni M, Sanhagi H, Zouari B, Kaabachi N, Ben Dridi MF: Incidence of mucopolysaccharidoses in Tunisia. Tunis Med. 2009, 87: 782-785.PubMed

10.

Neufeld EF, Muenzer J: The mucopolysaccharidoses. The Metabolic and Molecular Bases of Inherited Disease. Edited by: Scriver CR, Beaudet AL, Sly WS, Valle D. 1995, New York: McGraw-Hill, 2465-2494.

11.

Scott HS, Bunge S, Gal A, Clarke LA, Morris CP, Hopwood JJ: Molecular genetics of mucopolysaccharidosis type I: diagnostic, clinical, and biological implications. Hum Mutat. 1995, 6: 288-302. 10.1002/humu.1380060403.CrossRefPubMed

12.

Laradi S, Tukel T, Erazo M, Shabbeer J, Chkioua L, Khedhiri S, Ferchichi S, Chaabouni M, Miled A, Desnick RJ: Mucopolysaccharidosis I Alpha-L-Iduronidase mutations in three Tunisian families. J Inherit Metab Dis. 2005, 28: 1019-1026. 10.1007/s10545-005-0197-4.CrossRefPubMed

13.

Scott HS, Litjens T, Nelson PV, Brooks DA, Hopwood JJ, Morris CP: alpha-L-iduronidase mutations (Q70X and P533R) associate with a severe Hurler phenotype. Hum Mutat. 1992, 1: 333-339. 10.1002/humu.1380010412.CrossRefPubMed

14.

Alif N, Hess K, Straczek J, Sebbar S, N'Bou A, Nabet P, Dousset B: Mucopolysaccharidosis type I: characterization of a common mutation that causes Hurler syndrome in Moroccan subjects. Ann Hum Genet. 1999, 63: 9-16. 10.1046/j.1469-1809.1999.6310009.x.CrossRefPubMed

15.

Chkioua L, Khedhiri S, Jaidane Z, Ferchichi S, Habib S, Froissart R, Bonnet V, Chaabouni M, Dandana A, Jrad T, Limem H, Maire I, Abdelhedi M, Laradi S: Mucopolysaccharidosis type I: identification of alpha-L-iduronidase mutations in Tunisian families. Arch Pediatr. 2007, 14: 1183-9. 10.1016/j.arcped.2007.06.018.CrossRefPubMed

16.

Gatti R, DiNatale P, Villani GR, Filocamo M, Muller V, Guo XH, Nelson PV, Scott HS, Hopwood JJ: Mutations among Italian mucopolysaccharidosis type I patients. J Inherit Metab Dis. 1997, 20: 803-806. 10.1023/A:1005323918923.CrossRefPubMed

17.

Amr K, Katoury A, Abdel-Hamid M, Bassiouni R, Ibrahim M, Fateen E: Mutational Analysis of the alpha-L-iduronidase gene in three Egyptian families: identification of three novel mutations and five novel polymorphisms. Genet Test Mol Biomarkers. 2009, 13: 761-764. 10.1089/gtmb.2009.0057.CrossRefPubMed

18.

Levran O, Desnick RJ, Schuchman EH: Identification and expression of a common missense mutation (L302P) in the acid sphingomyelinase gene of Ashkenazi Jewish type A Niemann-Pick disease patients. Blood. 1992, 80: 2081-2087.PubMed

19.

Zlotogora J, Bach G, Bösenberg C, Barak Y, von Figura K, Gieselmann V: Molecular basis of late infantile metachromatic leukodystrophy in the Habbanite Jews. Hum Mutat. 1995, 5: 137-43. 10.1002/humu.1380050207.CrossRefPubMed

20.

Tuteja R, Bembi B, Agosti E, Baralle FE: 1448C mutation linked to the Pv1.1- genotype in Italian patients with Gaucher disease. Hum Mol Genet. 1993, 2: 781-4. 10.1093/hmg/2.6.781.CrossRefPubMed

21.

Yamagishi A, Tomatsu S, Fukuda S, Uchiyama A, Shimozawa N, Suzuki Y, Kondo N, Sukegawa K, Orii T: Mucopolysaccharidosis type I: identification of common mutations that cause Hurler and Scheie syndromes in Japanese populations. Hum Mutat. 1996, 7: 23-29. 10.1002/(SICI)1098-1004(1996)7:1<23::AID-HUMU3>3.0.CO;2-Q.CrossRefPubMed

22.

Matte U, Yogalingam G, Brooks D, Leistner S, Schwartz I, Lima L, Norato DY, Brum JM, Beesley C, Winchester B, Giugliani R, Hopwood JJ: Identification and characterization of 13 new mutations in mucopolysaccharidosis type I patients. Mol Genet Metab. 2003, 78: 37-43. 10.1016/S1096-7192(02)00200-7.CrossRefPubMed

23.

Bunge S, Kleijer WJ, Steglich C, Beck M, Zuther C, Morris CP, Schwinger E, Hopwood JJ, Scott HS, Gal A: Mucopolysaccharidosis type I: identification of 8 novel mutations and determination of the frequency of the two common alpha-L-iduronidase mutations (W402X and Q70X) among European patients. Hum Mol Genet. 1994, 3: 861-866. 10.1093/hmg/3.6.861.CrossRefPubMed

24.

Venturi N, Rovelli A, Parini R, Menni F, Brambillasca F, Bertagnolio F, Uziel G, Gatti R, Filocamo M, Donati MA, Biondi A, Goldwurm S: Molecular analysis of 30 mucopolysaccharidosis type I patients: evaluation of the mutational spectrum in Italian population and identification of 13 novel mutations. Hum Mutat. 2002, 20: 231-23.CrossRefPubMed

25.

Scott HS, Nelson PV, Litjens T, Hopwood JJ, Morris CP: Multiple polymorphisms within the alpha-L-iduronidase gene (IDUA): implications for a role in modification of MPS-I disease phenotype. Hum Mol Genet. 1993, 2: 1471-1473. 10.1093/hmg/2.9.1471.CrossRefPubMed

26.

Scott HS, Litjens T, Hopwood JJ, Morris CP: A common mutation for mucopolysaccharidosis type I associated with a severe Hurler syndrome phenotype. Hum Mutat. 1992, 1: 103-108. 10.1002/humu.1380010204.CrossRefPubMed

27.

Khedhiri S, Chkioua L, Ferchichi S, Miled A, Laradi S: Polymorphisms in Tunisian patients with N-acetylgalactosamine-6-sulfate sulfatase gene deficiency: Implication in Morquio A disease. Diagn Pathol. 2011, 6: 11-10.1186/1746-1596-6-11.PubMedCentralCrossRefPubMed

Title: Molecular analysis of mucopolysaccharidosis type I in Tunisia: identification of novel mutation and eight Novel polymorphisms
Authors: Latifa Chkioua
Souhir Khedhiri
Asma Kassab
Amina Bibi
Salima Ferchichi
Roseline Froissart
Christine Vianey-Saban
Sandrine Laradi
Abdelhedi Miled
Publication date: 01-12-2011
Publisher: BioMed Central
Published in: Diagnostic Pathology / Issue 1/2011
Electronic ISSN: 1746-1596
DOI: https://doi.org/10.1186/1746-1596-6-39

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Molecular analysis of mucopolysaccharidosis type I in Tunisia: identification of novel mutation and eight Novel polymorphisms

Abstract

Patients and methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Patients and methods

Results

Conclusion

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