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

Diagnostic Pathology

Abdelhedi Miled¹  Sandrine Laradi¹  Christine Vianey-Saban³  Roseline Froissart³  Salima Ferchichi¹  Amina Bibi²  Asma Kassab¹  Souhir Khedhiri¹  Latifa Chkioua¹ 

[1] Biology Molecular laboratory University of Pharmacy 5000 Monastir - Tunisia;Biology Molecular laboratory Child Hospital Tunis-Tunisia;Hereditary service of metabolic diseases and neonatal screening. Center of biology and pathology. 69677 BRON CEDEX France

关键词: Tunisian patients;    polymorphisms;    mutations;    IDUA gene;    Mucopolysaccharidosis type I;   

Others  :  809337
DOI  :  10.1186/1746-1596-6-39

 received in 2011-02-28, accepted in 2011-04-26,  发布年份 2011

【 摘 要 】

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.

【 授权许可】

   
2011 Latifa et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Neufeld EF, Muenzer J: The mucopolysaccharidoses. In The Metabolic and Molecular Bases of Inherited Disease. Edited by Scriver CR, Beaudet AL, Sly WS, Valle D. New York: McGraw-Hill; 2001:3421-3452.
• [2]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.
• [3]Scott HS, Guo XH, Hopwood JJ, Morris CP: Structure and sequence of the human alpha-L-iduronidase gene. Genomics 1992, 13:1311-1313.
• [4]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.
• [5]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.
• [6]Hartree EF: Determination of protein: a modification of the Lowry method that gives a linear photometric response. Anal Biochem 1972, 48:422-427.
• [7]Sambrook J, Fritisch EF, Maniatis T: Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York; 1989.
• [8]Nelson J: Incidence of the mucopolysaccharidoses in Northern Irland. Hum Genet 1997, 101:255-258.
• [9]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.
• [10]Neufeld EF, Muenzer J: The mucopolysaccharidoses. In The Metabolic and Molecular Bases of Inherited Disease. Edited by Scriver CR, Beaudet AL, Sly WS, Valle D. New York: McGraw-Hill; 1995:2465-2494.
• [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.
• [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.
• [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.
• [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.
• [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.
• [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.
• [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.
• [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.
• [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.
• [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.
• [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.
• [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.
• [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.
• [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.
• [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.
• [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.
• [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. BioMed Central Full Text