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Cloning of the sulphamidase gene and identification of mutations in Sanfilippo A syndrome

Abstract

Sanfilippo A syndrome is one of four recognised San-filippo sub-types (A, B, C and D) that result from deficiencies of different enzymes involved in the lysosomal degradation of heparan sulphate; patients suffer from severe neurological disorders. The Sanfilippo syndrome sub-types are also known as mucopolysaccharidosis (MRS) type III (MPS-IIIA, B, C and D), and are part of the large group of lysosomal storage disorders. Each of the MPS-III types is inherited as an autosomal recessive disorder with considerable variation in severity of clinical phenotype1. The incidence of Sanfilippo syndrome has been estimated at 1:24,000 in The Netherlands2 with MRS IIIA (MIM ♯252900) the most common. MPS-IIIA is the predominant MPS-III in the United Kingdom3, and has a similar high incidence to that found in The Netherlands (E. Wraith, personal communication). There is a particularly high incidence of a clinically severe form of MPS-IIIA in the Cayman Islands with a carrier frequency of 0.1 (ref. 4). Due to the mild somatic disease compared to other MRS disorders there is difficulty in diagnosing mild cases of MPS-III, hence Sanfilippo syndrome may be underdiagnosed, especially in patients with mild mental retardation1. Here, we report the isolation, sequence and expression of cDNA clones encoding the enzyme sulphamidase (EC 3.10.1.1). In addition, we report the chromosomal localisation of the sulphamidase gene as being 17q25.3. An 11-bp deletion, present in sulphamidase cDNA from two unrelated Sanfilippo A patients, is described.

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References

  1. Neufeld, E.F. & Muenzer, J. The mucopolysaccharidoses. In The metabolic and Molecular Basis of Inherited Disease, 2465–2494, 7th edn. Scriver, C.R., Beaudet A.L., Sly, W.S. & Valle, D., eds (McGraw-Hill, New York, 1995).

    Google Scholar 

  2. van de Kamp, J.J.P., Niermeijer, M.F., von Figura, K. & Giesberts, M.A.H. Genetic heterogeneity and clinical variability in the Sanfilippo syndrome (types A, B, and C). Clin. Genet. 20, 152–160 (1981).

    Article  CAS  Google Scholar 

  3. Whiteman, P. & Young, E. The laboratory diagnosis of Sanfilippo disease. Clin. Chem. Acta. 76, 139–147 (1977).

    Article  CAS  Google Scholar 

  4. Matalon, R.M., Deanching, M., Nakamura, F. & Bloom, A. A recessivery inherited lethal disease in a Caribbean isolate - A sulfamidase deficiency. Pediatr Res. 14, 524 (1980).

    Google Scholar 

  5. Hopwood, J.J. Enzymes that degrade heparin and heparan sulphate. In Heparin: Chemical and Bioiogical Properties, Clinical Applications. Lane, D.W. & Lindahieds, U., eds, 190–229 (Edward Arnold, London (1989).

    Google Scholar 

  6. Sanfilippo, S.J., Podosin, R., Langer, O., and Good, R.A. Merrtal retardation associated with acid mucoporysacchariduria (heparitin sulfate type). J. Pediat. 631, 837–838 (1963).

    Article  Google Scholar 

  7. Robertson, D.A., Freeman, C., Morris, C.R. & Hopwood, J.J. A cDNA clone for glucosamine-6-sulphatase reveals differences between aryl- and non-arylsulphatases. Biochem. J. 288, 539–544 (1992).

    Article  CAS  Google Scholar 

  8. Robertson, D.A., Freeman, C., Nelson, P.V., Morris, C.R. & Hopwood, J.J. Human glucosamine 6-sulphatase cDNA reveals homology with steroid sulphatase. Biochem. biophys. Res. Commun. 157, 218–224 (1988).

    Article  CAS  Google Scholar 

  9. Zhao, H.G., Lopez, R., Rennecker, J. & Neufeld, E.F. Sanfilippo syndrome B: cDNA and gene encoding human α-N-acetylglucosaminidase. Am. J. hum Genet. 55, 1473A (1994).

    Google Scholar 

  10. von Heijne, G. A new method for predicting signal sequence cleavage sites. Nucl. Acids Res. 14, 4683–4690 (1986).

    Article  CAS  Google Scholar 

  11. Freeman, C. & Hopwood, J.J. Human liver sulphamate sulphohydrolase: determination of native protein and subunit Mr values and influence of substrate agtycone structure on catalytic properties. Biochem. J. 234, 83–92 (1986).

    Article  CAS  Google Scholar 

  12. Rodewald, A. et al. A (1;21) balanced transtocatton in a mate with mucopdysaccharidosistype IIIA. Cytogenet Cell Genet. 27, 267 (1980).

    Article  CAS  Google Scholar 

  13. Saccone, S., De Sario, A., Valle, G.D. & Bernardi, G. The highest gene concentrations in the human genome are in tetomeric bands of metaphase chromosomes. Proc. natn. Acad. Sci. U.S.A. 89, 4913–4917 (1992).

    Article  CAS  Google Scholar 

  14. Midro, A.T., Debek, K., Sawicka, A., Marcinkiewicz, D. & Rogowska, M. Second observation of Silver-Russel (sic) syndrome in a carrier of a reciprocal translocation with one breakpoint at site 17q25. Clin. Genet. 44, 53–55 (1993).

    Article  CAS  Google Scholar 

  15. Lee, C.C. et al. Generation of cDNA probes directed by amino acid sequence: cloning of urateoxidase. Science 239, 1288–1291 (1988).

    Article  CAS  Google Scholar 

  16. Schuchman, E.H., Jackson, C.E. & Desnick, R.J. Human arylsulphatase B: MOPAC cloning, nucteotide sequence of a full length cDNA, and regions of amino acid identity with aryteulphatase A and C. Genomics 6, 149–158 (1990).

    Article  CAS  Google Scholar 

  17. Chen, Y.Q., Rafi, M A., deGala, G & Wenger, D.A. Cloning and expression of cDNA encoding human galactocerebrosidase, the enzyme deficient in globoid cell leukodystrophy. Hum. molec. Genet. 2, 1841–1845 (1993).

    Article  CAS  Google Scholar 

  18. Wilson, P.J. et al. Hunter syndrome: isolation of a cDNA clone encoding human iduronate-2-sulfatase and analysis of patient DNA. Proc. natn. Acad. Sci. U.S.A. 87, 8531–8535 (1990).

    Article  CAS  Google Scholar 

  19. Scott, H.S. et al. Human α-L-iduronidase: cDNA isolation and expression. Proc. natn. Acad. Sci. U.S.A. 88, 9695–9699 (1991).

    Article  CAS  Google Scholar 

  20. Callen, D.F. et al. Reassessment of two apparent deletions of chrosome16p to an ins(11;16) and a t(1;16) by chromosome painting. Ann. Genet. 33, 219–221 (1990).

    CAS  Google Scholar 

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Scott, H., Blanch, L., Guo, XH. et al. Cloning of the sulphamidase gene and identification of mutations in Sanfilippo A syndrome. Nat Genet 11, 465–467 (1995). https://doi.org/10.1038/ng1295-465

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