MUCOPOLYSACCHARIDOSIS IVA - A COMPARATIVE-STUDY OF POLYMORPHIC DNA HAPLOTYPES IN THE CAUCASIAN AND JAPANESE POPULATIONS

Mucopolysaccharidosis IVA (MPS IVA) is an autosomal recessive disorder caused by deficiency of the lysosomal enzyme N-acetylgalactosamine-6- sulphate sulphatase (GALNS). The genetic heterogeneity at the GALNS lo cus was studied in 62 mutant alleles and 376 normal alleles in the Cau casian population and also in 40 mutant and 100 normal alleles in the Japanese population. For this study, six different restriction fragmen t length polymorphisms (RFLPs) at the GALNS locus were analysed to sea rch for the frequency of each RFLP produced by StyI, SphI, RsaI, HaeII I, StuI and HapII restriction endonucleases. We detected a total of 27 haplotypes in the Caucasian and Japanese population. Of these 27 hapl otypes, 18 haplotypes were present in the Caucasian population and the most common of these was haplotype 1 (ABHcde) in both mutant and norm al alleles. In contrast, in the Japanese population we found 20 of the 27 haplotypes and the most common in mutant and normal alleles was ha plotype 2 (abhcDE). Within these two populations a parent in the MPS I VA family has an average probability of greater than 77% (in the Cauca sian population 77.27% and in the Japanese population 78.26%) of being heterozygous, and hence informative for linkage, at one or more GALNS RFLP sites. Our results delineate the molecular heterogeneity of MPS IVA haplotypes, as well as their significant interpopulation variation , and make prenatal diagnosis and carrier detection possible in the ma jority of families with one affected child.