Matte Ursula, Yogalingam Gouri, Brooks Doug, Leistner Sandra, Schwartz Ida, Lima Luciane, Norato Denise Y, Brum Jaime M, Beesley Clare, Winchester Bryan, Giugliani Roberto, Hopwood John J
Medical Genetics Service - Hospital de Clínicas de Porto Alegre, Porto Alegre RS, Brazil.
Mol Genet Metab. 2003 Jan;78(1):37-43. doi: 10.1016/s1096-7192(02)00200-7.
In this study we have investigated a group of 29 Brazilian patients, who had been diagnosed with the lysosomal storage disorder, Mucopolysaccharidosis type I (MPS-I). MPS I is caused by a deficiency in the lysosomal hydrolase, alpha-L-iduronidase. Ninety percent of the MPS I patients in this study were genotyped and revealed 10 recurrent and thirteen novel IDUA gene mutations. Eight of these new mutations and three common mutations W402X, P533R, and R383H were individually expressed in CHO-K1 cells and analyzed for alpha-L-iduronidase protein and enzyme activity. A correlation was observed between the MPS I patient clinical phenotype and the associated mutant alpha-L-iduronidase protein/enzyme activity expressed in CHO-K1 cells. This was the first time that Brazilian MPS I patients had been thoroughly analyzed and highlighted the difficulties of mutation screening and clinical phenotype assessment in populations with high numbers of unique mutations.
在本研究中，我们调查了一组29名巴西患者，他们被诊断患有溶酶体贮积症I型粘多糖病（MPS-I）。MPS I是由溶酶体水解酶α-L-艾杜糖醛酸酶缺乏引起的。本研究中90%的MPS I患者进行了基因分型，发现了10个复发突变和13个新的IDUA基因突变。其中8个新突变以及3个常见突变W402X、P533R和R383H分别在CHO-K1细胞中表达，并对α-L-艾杜糖醛酸酶蛋白和酶活性进行分析。观察到MPS I患者临床表型与CHO-K1细胞中表达的相关突变型α-L-艾杜糖醛酸酶蛋白/酶活性之间存在相关性。这是首次对巴西MPS I患者进行全面分析，并突出了在具有大量独特突变的人群中进行突变筛查和临床表型评估的困难。
