Functional analysis of the HGSNAT gene in patients with mucopolysaccharidosis IIIC (Sanfilippo C syndrome)

Anthony O. Fedele, John J. Hopwood

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12 Citations (Scopus)


Mucopolysaccharidosis (MPS) IIIC is an autosomal recessive lysosomal storage disorder caused by a deficiency in heparan acetyl CoA: α-glucosaminide N-acetyltransferase (HGSNAT). The characteristic feature is the deterioration of the central nervous system, but other symptoms may include coarse facies, developmental delay, macrocrania and motor retardation. HGSNAT is localised to the lysosomal membrane and catalyses a transmembrane acetylation in which the terminal glucosamine residue of heparan sulphate acquires an acetyl group, thus forming N-acetylglucosamine. 54 variants of the HGSNAT gene have been identified in MPS IIIC patients thus far, 22 of which are missense mutations. In this study, 20 of the latter were introduced into the cDNA of HGSNAT, and the resultant derivatives were exogenously expressed in cell culture. Transfection of 16 of these resulted in the synthesis of negligible HGSNAT protein and activity. The levels and function of the remaining 4 mutants, however, were similar to those of exogenously expressed wild-type HGSNAT. Interestingly, c.1209G>T (p.W403C), which is present in a variant classified in the former category, has only been sequenced in alleles also possessing c.1843G>A (p.A615T), which independently has a negligible effect on HGSNAT expression. This report suggests that these may function together to abolish HGSNAT activity.

Original languageEnglish
Pages (from-to)E1574-E1586
JournalHuman mutation
Issue number7
Publication statusPublished - 1 Jul 2010


  • Functional analysis
  • Mucopolysaccharidosis IIIC
  • Sanfilippo C syndrome

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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