Gene symbol: IDS. Disease: mucopolysaccharidosis type II (Hunter syndrome)

We report here the first exonic splicing mutation in a 8-year old intermediate Hunter patient. Genomic DNA sequencing identified a G to C transversion involving the last nucleotide of IDS exon VI (ExVI 1003G>C). The mutation leads to the disappearance of the normal exon VI/intron 6 splice donor site, resulting in the skipping of a 28 bp fragment of exon VI and in the production of a 306 aa mutant polypeptide, shorter than the normal protein (550 aa), differing from the wild type protein for the last 22 aa. A genotype-phenotype correlation is sometimes difficult in Hunter syndrome. However, the splicing mutations seem to correlate quite well to the patient’s phenotype: for instance, mutation G374G, a splicing site creating a mutation at codon 374 that leads to the loss of 20 aa, has been reported to be associated with mild phenotypes. Other alterations, i.e. the mutation described here and a Alu-mediated skipping of exon VIII, representing more severe genetic alterations, correlated well to the intermediate phenotypes of affected patients