Voskoboeva E Y, Krasnopolskaya X D, Mirenburg T V, Weber B, Hopwood J J
Research Centre for Medical Genetics, Moskvorechie 1, Moscow, Russia.
Mol Genet Metab. 1998 Oct;65(2):174-80. doi: 10.1006/mgme.1998.2745.
Mucopolysaccharidosis type I (MPS-I) is an autosomal recessive lysosomal storage disorder resulting from a deficiency of the lysosomal protein alpha-l-iduronidase (IDUA). Patients present within a broad spectrum of phenotypes from severe (Hurler syndrome) to clinically less severe (Scheie syndrome). Since 1982 a special program for the diagnosis and prevention of lysosomal storage diseases has operated in the former Soviet Union (FSU). We report the genotypes of 25 MPS-I patients with different clinical severities from the FSU. All the patients were screened for two common mutations (W402X and Q70X) and four other mutations (P533R, R89Q, A327P, 474 2a-->g). W402X and Q70X alleles accounted for 4 and 44%, respectively. Using SSCP analysis and subsequent direct sequencing we also detected four novel mutations (P533L, Q63X, Y343X, and A75P) in the IDUA gene, together with two mutations (974ins12bp, 134del12bp) described elsewhere. All were found in the heterozygous form in MPS-I patients with different clinical severities. A total of 32 mutant alleles leading to MPS-I was identified with nine patients fully genotyped. Four patients were homozygous for Q70X while five others were genetic compounds. Besides the eight identified mutations, six known polymorphisms were found. The spectrum of mutant alleles discovered is highly specific and proves the peculiarity of genetic loads in the FSU. Our data suggest a closer relationship between the FSU and Scandinavian populations than with Western and Central European populations.
I型黏多糖贮积症（MPS-I）是一种常染色体隐性溶酶体贮积病，由溶酶体蛋白α-L-艾杜糖醛酸酶（IDUA）缺乏引起。患者表现出广泛的表型，从严重型（Hurler综合征）到临床症状较轻型（Scheie综合征）。自1982年以来，前苏联开展了一项诊断和预防溶酶体贮积病的特别项目。我们报告了来自前苏联的25例不同临床严重程度的MPS-I患者的基因型。对所有患者筛查了两个常见突变（W402X和Q70X）以及其他四个突变（P533R、R89Q、A327P、474 2a-->g）。W402X和Q70X等位基因分别占4%和44%。通过单链构象多态性分析（SSCP）及随后的直接测序，我们还在IDUA基因中检测到四个新突变（P533L、Q63X、Y343X和A75P），以及其他地方描述的两个突变（974ins12bp、134del12bp）。所有这些突变均在不同临床严重程度的MPS-I患者中以杂合形式被发现。共鉴定出32个导致MPS-I的突变等位基因，其中9例患者进行了全基因分型。4例患者为Q70X纯合子，另外5例为基因复合杂合子。除了已鉴定的8个突变外，还发现了6个已知的多态性位点。所发现的突变等位基因谱具有高度特异性，证明了前苏联人群遗传负荷的特殊性。我们的数据表明，前苏联人群与斯堪的纳维亚人群的关系比与西欧和中欧人群的关系更为密切。
