Mucopolysaccharidosis IVA: screening and identification of mutations of the N-acetylgalactosamine-6-sulfate sulfatase gene

Mutations causing mucopolysaccharidosis IVA in 15 Japanese andone Caucasian patient were characterized. To screen these mutations,we used a combination of single strand conformation polymorphismanalysis and heteroduplex analysis for PCR products of targetedcDNA or genomic DNA. Various small mutations were identifiedin 23 of 26 alleles, while the other six alleles had large rearrangements.Cycle sequencing of PCR products revealed 15 different mutations,including 12 missense, one nonsense, one frame shift (2 bp deletion)and one splice site mutation, in accord with the broad rangeof clinical phenotypes. Two alleles have different mutationsin the same nucleotide position of exon 3 (R94C, CGC