Molecular analysis of Sanfilippo syndrome type C in Spain: seven novel HGSNAT mutations and characterization of the mutant alleles

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 [mucopolysacch...

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Published in:	Clinical genetics Vol. 80; no. 4; pp. 367 - 374
Main Authors:	Canals, I, Elalaoui, SC, Pineda, M, Delgadillo, V, Szlago, M, Jaouad, IC, Sefiani, A, Chabás, A, Coll, MJ, Grinberg, D, Vilageliu, L
Format:	Journal Article
Language:	English
Published:	Oxford, UK Blackwell Publishing Ltd 01-10-2011 Wiley-Blackwell
Subjects:	Acetyltransferases - genetics Alleles Biological and medical sciences Canals Carbohydrates (enzymatic deficiencies). Glycogenosis Child Child, Preschool Enzymes Errors of metabolism Exons Female Fibroblasts Fundamental and applied biological sciences. Psychology Gene Expression General aspects. Genetic counseling Genes Genetic disorders Genetics of eukaryotes. Biological and molecular evolution haplotype analysis Haplotypes Heparan sulfate heterologous expression HGSNAT gene Humans Introns Male Medical genetics Medical sciences Metabolic diseases Metabolic disorders Missense mutation Molecular and cellular biology Mucopolysaccharidosis Mucopolysaccharidosis III - diagnosis Mucopolysaccharidosis III - genetics mucopolysaccharidosis IIIC Mutation mutations Pathogenesis Point mutation Polymorphism, Single Nucleotide RNA RNA Splicing Single-nucleotide polymorphism Spain Splicing Europe Spain Human haplotype analysis Diseases of the osteoarticular system Metabolic diseases Mucopolysaccharidosis heterologous expression Gene expression Enzymopathy Genetic disease Characterization Allele HGSNAT gene mutations Gene Genetics mucopolysaccharidosis IIIC Carbohydrate Mutation Haplotype
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Summary:	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.
Bibliography:	ArticleID:CGE1525 ark:/67375/WNG-5MGNZP74-H istex:253FC01F163DDBB20B007ACE2D89FAC9D71F236A ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1
ISSN:	0009-9163 1399-0004
DOI:	10.1111/j.1399-0004.2010.01525.x