Kato Z, Fukuda S, Tomatsu S, Vega H, Yasunaga T, Yamagishi A, Yamada N, Valencia A, Barrera L A, Sukegawa K, Orii T, Kondo N
Department of Pediatrics, Gifu University School of Medicine, Japan.
Hum Genet. 1997 Nov;101(1):97-101. doi: 10.1007/s004390050594.
Mucopolysaccharidosis IVA (MPS IVA) is an autosomal recessive lysosomal storage disorder caused by a genetic defect in N-acetylgalactosamine-6-sulfate sulfatase (GALNS). In previous studies, we have found two common mutations in Caucasians and Japanese, respectively. To characterize the mutational spectrum in various ethnic groups, mutations in the GALNS gene in Colombian MPS IVA patients were investigated, and genetic backgrounds were extensively analyzed to identify racial origin, based on mitochondrial DNA (mtDNA) lineages. Three novel missense mutations never identified previously in other populations and found in 16 out of 19 Colombian MPS IVA unrelated alleles account for 84.2% of the alleles in this study. The G301C and S162F mutations account for 68.4% and 10.5% of mutations, respectively, whereas the remaining F69V is limited to a single allele. The skewed prevalence of G301C in only Colombian patients and haplotype analysis by restriction fragment length polymorphisms in the GALNS gene suggest that G301C originated from a common ancestor. Investigation of the genetic background by means of mtDNA lineages indicate that all our patients are probably of native American descent.
黏多糖贮积症IVA（MPS IVA）是一种常染色体隐性溶酶体贮积病，由N-乙酰半乳糖胺-6-硫酸酯硫酸酯酶（GALNS）的基因缺陷引起。在之前的研究中，我们分别在白种人和日本人中发现了两种常见突变。为了表征不同种族的突变谱，我们对哥伦比亚MPS IVA患者的GALNS基因中的突变进行了研究，并基于线粒体DNA（mtDNA）谱系对遗传背景进行了广泛分析，以确定种族起源。在19个哥伦比亚MPS IVA无关等位基因中，有16个发现了3种此前在其他人群中从未发现过的新错义突变，占本研究中等位基因的84.2%。G301C和S162F突变分别占突变的68.4%和10.5%，而其余的F69V仅存在于一个等位基因中。仅在哥伦比亚患者中G301C的患病率偏高，以及通过GALNS基因的限制性片段长度多态性进行单倍型分析表明，G301C起源于一个共同祖先。通过mtDNA谱系对遗传背景进行调查表明，我们所有的患者可能都是美洲原住民后裔。
