Consortium for Human Molecular Genetics, Milano Bicocca University, Monza, Italy.
Hum Mutat. 2011 Jun;32(6):E2189-210. doi: 10.1002/humu.21479. Epub 2011 Mar 10.
Mutational analysis of the IDUA gene was performed in a cohort of 102 European patients with mucopolysaccharidosis type I. A total of 54 distinct mutant IDUA alleles were identified, 34 of which were novel including 12 missense mutations, 2 nonsense mutations, 12 splicing mutations, 5 micro-deletions, 1 micro-duplication 1 translational initiation site mutation, and 1 'no-stop' change (p.X654RextX62). Evidence for the pathological significance of all novel mutations identified was sought by means of a range of methodological approaches, including the assessment of evolutionary conservation, RT-PCR/in vitro splicing analysis, MutPred analysis and visual inspection of the 3D-model of the IDUA protein. Taken together, these data not only demonstrate the remarkable mutational heterogeneity characterizing type 1 mucopolysaccharidosis but also illustrate our increasing ability to make deductions pertaining to the genotype-phenotype relationship in disorders manifesting a high degree of allelic heterogeneity.
对 102 名患有黏多糖贮积症 I 型的欧洲患者的 IDUA 基因进行了突变分析。共鉴定出 54 种不同的突变 IDUA 等位基因，其中 34 种是新的，包括 12 种错义突变、2 种无义突变、12 种剪接突变、5 种微缺失、1 种微重复、1 种翻译起始位点突变和 1 种“无终止”改变（p.X654RextX62）。通过一系列方法，包括评估进化保守性、RT-PCR/体外剪接分析、MutPred 分析和 IDUA 蛋白三维模型的直观检查，寻找所有新鉴定的突变的病理意义的证据。这些数据不仅表明 1 型黏多糖贮积症的突变高度异质性，还说明了我们在表现出高度等位基因异质性的疾病中，推断基因型-表型关系的能力不断增强。
