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

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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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Authors and Affiliations

  1. Lysosomal Diseases Research Unit, Department of Chemical Pathology, Women's and Children's Hospital, North Adelaide, S.A., 5006, Australia

    Hamish S. Scott, Lianne Blanch, Xiao-Hui Guo, Annette Orsborn, C. Phillip Morris & John J. Hopwood

  2. Division of Cell Biology, John Curtin School of Medical Research, The Australian National University, Canberra, ACT, 2601, Australia

    Craig Freeman

  3. Department of Cytogenetics and Molecular Genetics, Women's and Children's Hospital, North Adelaide, S.A., 5006, Australia

    Elizabeth Baker & Grant R. Sutherland

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  1. Hamish S. Scott
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  2. Lianne Blanch
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  3. Xiao-Hui Guo
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  4. Craig Freeman
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  5. Annette Orsborn
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  6. Elizabeth Baker
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  7. Grant R. Sutherland
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  8. C. Phillip Morris
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  9. John J. Hopwood
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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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  • DOI: https://doi.org/10.1038/ng1295-465

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