Molecular analysis of Sanfilippo syndrome type C in Spain: seven novel HGSNAT mutations and characterization of the mutant alleles
Article first published online: 2 AUG 2010
© 2010 John Wiley & Sons A/S
Volume 80, Issue 4, pages 367–374, October 2011
How to Cite
Canals, I., Elalaoui, S., Pineda, M., Delgadillo, V., Szlago, M., Jaouad, I., Sefiani, A., Chabás, A., Coll, M., Grinberg, D. and Vilageliu, L. (2011), Molecular analysis of Sanfilippo syndrome type C in Spain: seven novel HGSNAT mutations and characterization of the mutant alleles. Clinical Genetics, 80: 367–374. doi: 10.1111/j.1399-0004.2010.01525.x
- Issue published online: 8 SEP 2011
- Article first published online: 2 AUG 2010
- Accepted manuscript online: 2 AUG 2010 12:00AM EST
- Received 10 June 2010, revised and accepted for publication 27 July 2010
- haplotype analysis;
- heterologous expression;
- HGSNAT gene;
- mucopolysaccharidosis IIIC;
Canals I, Elalaoui SC, Pineda M, Delgadillo V, Szlago M, Jaouad IC, Sefiani A, Chabás A, Coll MJ, Grinberg D, Vilageliu L. Molecular analysis of Sanfilippo syndrome type C in Spain: seven novel HGSNAT mutations and characterization of the mutant alleles.
The Sanfilippo syndrome type C [mucopolysaccharidosis IIIC (MPS IIIC)] is caused by mutations in the HGSNAT gene, encoding an enzyme involved in heparan sulphate degradation. We report the first molecular study on several Spanish Sanfilippo syndrome type C patients. Seven Spanish patients, one Argentinean and three Moroccan patients were analysed. All mutant alleles were identified and comprised nine distinct mutant alleles, seven of which were novel, including four missense mutations (p.A54V, p.L113P, p.G424V and p.L445P) and three splicing mutations due to two point mutations (c.633+1G>A and c.1378-1G>A) and an intronic deletion (c.821-31_821-13del). Furthermore, we found a new single nucleotide polymorphism (SNP) (c.564-98T>C). The two most frequent changes were the previously described c.372-2A>G and c.234+1G>A mutations. All five splicing mutations were experimentally confirmed by studies at the RNA level, and a minigene experiment was carried out in one case for which no fibroblasts were available. Expression assays allowed us to show the pathogenic effect of the four novel missense mutations and to confirm that the already known c.710C>A (p.P237Q) is a non-pathogenic SNP. Haplotype analyses suggested that the two mutations (c.234+1G>A and c.372-2A>G) that were present in more than one patient have a common origin, including one (c.234+1G>A) that was found in Spanish and Moroccan patients.