title: Mucopolysaccharidosis IVA: polymorphic haplotypes and informative RFLPs in the Japanese population.
abstract: Seven different restriction fragment length polymorphisms (RFLPs) at the N-acetylgalactosamine-6-sulfate sulfatase (GALNS) locus were analyzed using Southern blotting and polymerase chain reaction based techniques to search for the frequency of each RFLP produced by StyI, SphI, HaeIII, StuI, HapII, XhoI, and BamHI restriction endonucleases, respectively, in 36 mutant alleles, including two sibling cases and 100 normal alleles. Calculation of heterozygosity indexes showed that these RFLPs were polymorphic, ranging from 0.31 to 0.69 in mucopolysaccharidosis IVA (MPS IVA) patients compared with 0.21 to 0.65 in normal individuals. There was some significant difference in several RFLPs and in the combination with four kinds of RFLPs (SphI, StuI, HapII, XhoI polymorphisms). The normal alleles were composed of 13 different RFLPs haplotypes; the most common among the Japanese population carrying normal alleles was haplotype 8 (bDEF1) (31.3%), the others being dispersed. The same haplotype 8 was the most frequent in the mutant alleles (44.4%), with seven further haplotypes. These findings revealed the striking variety of polymorphic haplotypes in the MPS IVA gene. By using these five kinds of RFLPs, we examined the theoretical informativity of haplotype analysis in heterozygote detection in nine unrelated MPS IVA families and ten unrelated normal families. All the members of the MPS IVA families studied were diagnosed as a patient, carrier, or non-carrier. We propose that prenatal diagnosis or family analysis in cases in which mutations have not been characterized is now feasible.
authors.affiliation: Department of Pediatrics, Gifu University School of Medicine, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Iwata
authors.forename: S
authors.initials: S
authors.lastname: Tomatsu
authors.forename: S
authors.initials: S
authors.lastname: Fukuda
authors.forename: A
authors.initials: A
authors.lastname: Uchiyama
authors.forename: G M
authors.initials: GM
authors.lastname: Rezvi
authors.forename: T
authors.initials: T
authors.lastname: Ogawa
authors.forename: T
authors.initials: T
authors.lastname: Hori
authors.forename: Y
authors.initials: Y
authors.lastname: Nakashima
authors.forename: A
authors.initials: A
authors.lastname: Yamagishi
authors.forename: K
authors.initials: K
authors.lastname: Sukegawa
mesh_terms: D001483:Base Sequence; D016009:Chi-Square Distribution; D017931:DNA Primers; D015245:Deoxyribonuclease BamHI; D019003:Deoxyribonuclease HpaII; D015252:Deoxyribonucleases, Type II Site-Specific; D005260:Female; D005787:Gene Frequency; D006580:Genetic Carrier Screening; D006239:Haplotypes; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D018598:Minisatellite Repeats; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D009085:Mucopolysaccharidosis IV / Q000453:epidemiology / Q000235:genetics*; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D017931:DNA Primers; D015245:Deoxyribonuclease BamHI; D019003:Deoxyribonuclease HpaII; C046184:endodeoxyribonuclease PaeI; C028868:AGGCCT-specific type II deoxyribonucleases; C034510:CTCGAG-specific type II deoxyribonucleases; D015252:Deoxyribonucleases, Type II Site-Specific