Rezvi G M, Tomatsu S, Fukuda S, Yamagishi A, Cooper A, Wraith J E, Iwata H, Kato Z, Yamada N, Sukegawa K, Shimozawa N, Suzuki Y, Kondo N, Orii T
Department of Pediatrics, Gifu University School of Medicine, Japan.
J Inherit Metab Dis. 1996;19(3):301-8. doi: 10.1007/BF01799258.
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 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 by StyI, SphI, RsaI, HaeIII, StuI and HapII 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.
粘多糖贮积症IVA型（MPS IVA）是一种常染色体隐性疾病，由溶酶体酶N - 乙酰半乳糖胺 - 6 - 硫酸酯硫酸酯酶（GALNS）缺乏引起。我们对白种人群中的62个突变等位基因和376个正常等位基因，以及日本人群中的40个突变等位基因和100个正常等位基因进行了GALNS基因座的遗传异质性研究。在这项研究中，分析了GALNS基因座的六种不同限制性片段长度多态性（RFLP），以寻找由StyI、SphI、RsaI、HaeIII、StuI和HapII限制性内切酶产生的每种RFLP的频率。我们在白种人和日本人群中总共检测到27种单倍型。在这27种单倍型中，18种存在于白种人群中，其中最常见的是突变等位基因和正常等位基因中的单倍型1（ABHcde）。相比之下，在日本人群中，我们在27种单倍型中发现了20种，突变等位基因和正常等位基因中最常见的是单倍型2（abhcDE）。在这两个人群中，MPS IVA家族中的一位亲本在一个或多个GALNS RFLP位点杂合的平均概率大于77%（白种人群中为77.27%，日本人群中为78.26%），因此对连锁分析具有信息价值。我们的结果描绘了MPS IVA单倍型的分子异质性及其显著的群体间差异，并使得在大多数有一个患病孩子的家庭中进行产前诊断和携带者检测成为可能。
