Hunter disease in the Spanish population: Molecular analysis in 31 families
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Mucopolysaccharidosis type II (Hunter disease) is an X-linked disorder due to deficiency of the lysosomal enzyme iduronate 2-sulphatase. Here we report an update of molecular studies in 31 Spanish families with Hunter disease. We found a total of 22 novel small mutations (7 reported previously by our group), and 4 large deletions or rearrangements. Particularly relevant are two mutations, one showing an alternatively spliced product although the normal splice site is conserved; the other mutation results in an amino acid change that most likely modifies regulation of expression of the IDS gene. Except for large gene alterations and for the G374sp mutation already described, we could not establish a clear phenotype–genotype correlation. Mutation G374sp is the point mutation most frequent in our population (10%) and is always associated with mild phenotype. Our molecular analyses carried out in a relatively large series of patients with Hunter disease contribute to the identification of new mutations and reinforce the conclusions drawn in other populations about the genotype–phenotype correlation and the gene distribution of mutations.
- Ben Simon-Schi. E, Bache G, Hopwood JJ, Abeliovich D (1994) Mutation analysis of Jewish Hunter patients in Israel. Hum Mutat 4: 263-270.
- Bondeson ML, Dahl N, Malmgren H, et al (1995) Inversion of the IDS gene resulting from recombination with IDS-related sequences is a common cause of the Hunter syndrome. Hum Mol Genet 4: 615-621.
- Bunge S, Steglich C, Zuther C, et al (1993) Iduronate-2-sulfatase gene mutations in 16 patients with mucopolysaccharidosis type II (Hunter syndrome). Hum Mol Genet 2: 1871-1875.
- Flomen RH, Green EP, Green PM, Bentley DR, Gianelli F (1993) Determination of the organisation of coding sequences within the iduronate sulphate sulphatase (IDS) gene. Hum Mol Genet 2: 5-10.
- Goldenfum SL, Young E, Michelakakis H, Tsagarakis S, Winchester B (1996) Mutation analysis in 20 patients with Hunter disease. Hum Mutat 7: 76-78.
- Gort L, Coll MJ, Chabás A (1998) Mutations in the iduronate-2-sulfatase gene in 12 Spanish patients with Hunter disease. Hum Mutat (supplement 1): S66-S68.
- Hopwood JJ, Bunge S, Morris CP, et al (1993) Molecular basis of mucopolysaccharidosis type II: mutations in the iduronate-2-sulphatase gene. Hum Mutat 2: 435-442.
- Lagerstedt K, Karsten SL, Carlberg BM, et al (1997) Double-strand breaks may initiate the inversion mutation causing the Hunter syndrome. Hum Mol Genet 6: 627-633.
- Lewin B (1990) The assembly line for protein synthesis. In Genes IV. Oxford: Oxford University Press: 113-135.
- Lissens W, Seneca S, Liebaers I (1997) Molecular analysis in 23 Hunter disease families. J Inher Metab Dis 20: 453-456.
- Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16: 1215.
- Olsen TC, Eiken HG, Knappskog PM, et al (1996) Mutations in the iduronate-2-sulfatase gene in five Norwegians with Hunter syndrome. Hum Genet 97: 198-203.
- Palmieri G, Capra V, Romano G, et al (1992) The iduronate sulfatase gene: isolation of a 1.2-Mb YAC contig spanning the entire gene and identification of heterogeneous deletions in patients with Hunter syndrome. Genomics 12: 52-57.
- Popowska E, Rathmann M, Tylki-Szymanska A, et al (1995) Mutations of the iduronate-2-sulfatase gene in 12 Polish patients with mucopolysaccharidosis type II (Hunter syndrome). Hum Mutat 5: 97-100.
- Rathmann M, Bunge S, Beck M, Kresse H, Tylki-Szymanska A, Gal A (1996) Mucopolysac-charidosis type II (Hunter syndrome): mutation ‘hot spots’ in the iduronate-2-sulfatase gene. Am J Hum Genet 59: 1202-1209.
- Sanger F, Nicklen S, Coulson AR (1977) DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci USA 74: 5463-5467.
- Steén-Bondeson ML, Dahl N, Tönnesen T, et al (1992) Molecular analysis of patients with Hunter syndrome: implication of a region prone to structural alterations within the IDS gene. Hum Mol Genet 1: 195-198.
- Wilson PJ, Morris CP, Anson DS, et al (1990) Hunter syndrome: isolation of an iduronate-2-sulfatase cDNA clone and analysis of patient DNA. Proc Natl Acad Sci USA 87: 8531-8535.
- Wilson PJ, Meaney CA, Hopwood JJ, Morris CP (1993) Sequence of the human iduronate 2-sulfatase (IDS) gene. Genomics 17: 773-775.
- Yamada Y, Tomatsu S, Sukegawa K, et al (1993) Mucopolysaccharidosis type II (Hunter disease): 13 gene mutations in 52 Japanese patients and carrier detection in four families. Hum Genet 92: 110-114.
- Hunter disease in the Spanish population: Molecular analysis in 31 families
Journal of Inherited Metabolic Disease
Volume 21, Issue 6 , pp 655-661
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