Prommajan Korrakot, Ausavarat Surasawadee, Srichomthong Chalurmpon, Puangsricharern Vilavun, Suphapeetiporn Kanya, Shotelersuk Vorasuk
1Center of Excellence for Medical Genetics, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Mol Vis. 2011 Feb 11;17:456-60.
To characterize the pathogenic mutations causing mucopolysaccharidosis type I (MPS I) in two Thai patients: one with Hurler syndrome (MPS IH), the most severe form, and the other with Scheie syndrome (MPS IS), the mildest. Both presented with distinctive phenotype including corneal clouding.
The entire coding regions of the α-L-iduronidase (IDUA) gene were amplified by PCR and sequenced. Functional characterization of the mutant IDUA was determined by transient transfection of the construct into COS-7 cells.
Mutation analyses revealed that the MPS IH patient was homozygous for a previously reported mutation, c.252insC, while the MPS IS patient was found to harbor a novel c.826G>A (p.E276K) mutation. The novel p.E276K mutation was not detected in 100 unaffected ethnic-matched control chromosomes. In addition, the glutamic acid residue at codon 276 was located at a well conserved residue. Transient transfection of the p.E276K construct revealed a significant reduction of IDUA activity compared to that of the wild-type IDUA suggesting it as a disease-causing mutation.
This study reports a novel mutation, expanding the mutational spectrum for MPS I.
鉴定导致两名泰国患者患I型黏多糖贮积症（MPS I）的致病突变：一名患有最为严重的Hurler综合征（MPS IH），另一名患有最为轻微的Scheie综合征（MPS IS）。两名患者均表现出包括角膜混浊在内的独特表型。
通过聚合酶链反应（PCR）扩增α-L-艾杜糖醛酸酶（IDUA）基因的整个编码区并进行测序。通过将构建体瞬时转染到COS-7细胞中来确定突变型IDUA的功能特性。
突变分析显示，MPS IH患者对于先前报道的突变c.252insC呈纯合状态，而MPS IS患者被发现携带一种新的c.826G>A（p.E276K）突变。在100条未受影响的种族匹配对照染色体中未检测到新的p.E276K突变。此外，第276密码子处的谷氨酸残基位于一个高度保守的残基位置。与野生型IDUA相比，p.E276K构建体的瞬时转染显示IDUA活性显著降低，表明其为致病突变。
本研究报告了一种新的突变，扩大了MPS I的突变谱。
