HUNTER-DISEASE IN THE SPANISH POPULATION - MOLECULAR ANALYSIS IN 31 FAMILIES

Mucopolysaccharidosis type II (Hunter disease) is an X-linked disorder due to deficiency of the lysosomal enzyme iduronate 2-sulphatase. Her e we report an update of molecular studies in 31 Spanish families with Hunter disease. We found a total of 22 novel small mutations (7 repor ted 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 oth er mutation results in an amino acid change that most likely modifies regulation of expression of the IDS gene. Except for large gene altera tions and for the G374sp mutation already described, we could not esta blish a clear phenotype-genotype correlation. Mutation G374sp is the p oint mutation most frequent in our population (10%) and is always asso ciated with mild phenotype. Our molecular analyses carried out in a re latively large series of patients with Hunter disease contribute to th e identification of new mutations and reinforce the conclusions drawn in other populations about the genotype-phenotype correlation and the gene distribution of mutations.