Article

Journal of Inherited Metabolic Disease

, Volume 19, Issue 3, pp 301-308

First online:

Mucopolysaccharidosis IVA: a comparative study of polymorphic DNA haplotypes in the Caucasian and Japanese populations

  • G. M. M. RezviAffiliated withDepartment of Pediatrics, Gifu University School of Medicine
  • , S. TomatsuAffiliated withDepartment of Pediatrics, Gifu University School of Medicine
  • , S. FukudaAffiliated withDepartment of Pediatrics, Gifu University School of Medicine
  • , A. YamagishiAffiliated withDepartment of Pediatrics, Gifu University School of Medicine
  • , A. CooperAffiliated withRoyal Manchester Children's Hospital
  • , J. E. WraithAffiliated withRoyal Manchester Children's Hospital
  • , H. IwataAffiliated withDepartment of Pediatrics, Gifu University School of Medicine
  • , Z. KatoAffiliated withDepartment of Pediatrics, Gifu University School of Medicine
  • , N. YamadaAffiliated withDepartment of Pediatrics, Gifu University School of Medicine
    • , K. SukegawaAffiliated withDepartment of Pediatrics, Gifu University School of Medicine
    • , N. ShimozawaAffiliated withDepartment of Pediatrics, Gifu University School of Medicine
    • , Y. SuzukiAffiliated withDepartment of Pediatrics, Gifu University School of Medicine
    • , N. KondoAffiliated withDepartment of Pediatrics, Gifu University School of Medicine
    • , T. OriiAffiliated withDepartment of Pediatrics, Gifu University School of Medicine

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

Summary

Mucopolysaccharidosis IVA (MPS IVA) is an autosomal recessive disorder caused by deficiency of the lysosomal enzymeN-acetylgalactosamine-6-sulphate sulphatase (GALNS). The genetic heterogeneity at the GALNS locus was studied in 62 mutant alleles and 376 normal alleles in the Caucasian population and also in 40 mutant and 100 normal alleles in the Japanese population. For this study, six different restriction fragment length polymorphisms (RFLPs) at the GALNS locus were analysed to search for the frequency of each RFLP produced byStyI,SphI,RsaI,HaeIII,StuI andHapII restriction endonucleases. We detected a total of 27 haplotypes in the Caucasian and Japanese population. Of these 27 haplotypes, 18 haplotypes were present in the Caucasian population and the most common of these was haplotype 1 (ABHcde) in both mutant and normal alleles. In contrast, in the Japanese population we found 20 of the 27 haplotypes and the most common in mutant and normal alleles was haplotype 2 (abhcDE). Within these two populations a parent in the MPS IVA family has an average probability of greater than 77% (in the Caucasian 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 majority of families with one affected child.