Another Novel Missense Mutation in ARSB Gene in Iran
Mucopolysaccharidosis VI (MPS-VI) is an infrequent autosomal recessive disorder caused by mutations in ARSB gene and deficiency in lysosomal enzyyme ARSB activities subsequently. This enzyme is essential for the breaking of glycosaminoglycans (GAGs) such as dermatan sulfate and chondroitin sulfate. ARSB dysfunction results in imperfect breakdown of GAGs and their accumulation in urine. Mutations in ARSB gene are the main players in MPS-VI disease and its clinical consequences. Most reported mutations are point mutations but there are some other examples in literature. Here we report a novel missense mutation in ARSB gene that is inherited as an autosomal recessive mode and probably explain the clinical status of the proband. This mutation replaces the threonine 92 by proline and alters ARSB structure. This is the most feasible scenario for clinical condition we described here. This novel mutation should be remarked for PND and PGD to improve the health and management of such families.
Black SH, Pelias MZ, Miller JB, Blitzer MG, Shapira E. Maroteaux-Lamy syndrome in a large consanguineous kindred: biochemical and immunological studies. Am J Med Genet 1986;25:273-9.
Maroteaux P, Leveque B, Marie J, Lamy M. A New Dysostosis With Urinary Elimination of Chondroitin Sulfate B. La Presse medicale 1963;711849-52.
Nelson J, Crowhurst J, Carey B, Greed L. Incidence of the mucopolysaccharidoses in Western Australia. American journal of medical genetics Part A 2003;123a:310-3.
Peterson DI, Bacchus H, Seaich L, Kelly TE. Myelopathy associated with Maroteaux-Lamy syndrome. Arch Neurol 1975;32:127-9.
Young R, Kleinman G, Ojemann RG, Kolodny E, Davis K, Halperin J, et al. Compressive myelopathy in Maroteaux-Lamy syndrome: clinical and pathological findings. Ann Neurol 1980;8:336-40.
Azevedo AC, Schwartz IV, Kalakun L, Brustolin S, Burin MG, Beheregaray AP, et al. Clinical and biochemical study of 28 patients with mucopolysaccharidosis type VI. Clin Genet 2004;66:208-13.
Vestermark S, Tonnesen T, Andersen MS, Guttler F. Mental retardation in a patient with Maroteaux-Lamy. Clin Genet 1987;31:114-7.
Valayannopoulos V, Nicely H, Harmatz P, Turbeville S. Mucopolysaccharidosis VI. Orphanet J Rare Dis 2010;55.
Litjens T, Baker EG, Beckmann KR, Morris CP,Hopwood JJ, Callen DF. Chromosomal localization of ARSB, the gene for human N-acetylgalactosamine-4-sulphatase. Hum Genet 1989;82:67-8.
Karageorgos L, Brooks DA, Pollard A, Melville EL, HeinLK, Clements PR, et al. Mutational analysis of 105mucopolysaccharidosis type VI patients. Hum Mutat2007;28:897-903.
Wicker G, Prill V, Brooks D, Gibson G, Hopwood J, vonFigura K, et al. Mucopolysaccharidosis VI (Maroteaux-Lamy syndrome). An intermediate clinical phenotypecaused by substitution of valine for glycine at position137 of arylsulfatase B. J Biol Chem 1991;266:21386-91.
Jin WD, Jackson CE, Desnick RJ, Schuchman EH.Mucopolysaccharidosis type VI: identification of threemutations in the arylsulfatase B gene of patients with thesevere and mild phenotypes provides molecular evidencefor genetic heterogeneity. Am J Hum Genet 1992;50:795-800.
Litjens T, Brooks DA, Peters C, Gibson GJ, Hopwood JJ.Identification, expression, and biochemicalcharacterization of Nacetylgalactosamine-4-sulfatasemutations and relationship with clinical phenotype inMPS-VI patients. Am J Hum Genet 1996;58:1127-34.
Litjens T, Hopwood JJ. Mucopolysaccharidosis type VI:Structural and clinical implications of mutations in Nacetylgalactosamine-4-sulfatase. Hum Mutat2001;18:282-95.
Villani GR, Balzano N, Vitale D, Saviano M, Pavone V,Di Natale P. Maroteaux-lamy syndrome: five novelmutations and their structural localization. BiochimBiophys Acta 1999;1453:185-92.
Bhattacharyya S, Kotlo K, Danziger R, Tobacman JK.Arylsulfatase B regulates interaction of chondroitin-4-sulfate and kininogen in renal epithelial cells. BiochimBiophys Acta 2010;1802:472-7.
Brooks DA, McCourt PA, Gibson GJ, Hopwood JJ.Immunoquantification of the low abundance lysosomalenzyme Nacetylgalactosamine 4-sulphatase. J InheritMetab Dis 1990;13:108-20.
Brooks DA, McCourt PA, Gibson GJ, Ashton LJ, ShutterM, Hopwood JJ. Analysis of N-acetylgalactosamine-4-sulfatase protein and kinetics in mucopolysaccharidosistype VI patients. Am J Hum Genet 1991;48:710-9.
Parenti G, Meroni G, Ballabio A. The sulfatase genefamily. Curr Opin Genet Dev 1997;7:386-91.
Vairo F, Federhen A, Baldo G, Riegel M, Burin M,Leistner-Segal S, et al. Diagnostic and treatmentstrategies in mucopolysaccharidosis VI. Appl Clin Genet2015;8245-55.
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