两种导致法布里病的新型α-半乳糖苷酶 A 突变：杂合子女性中的错义突变 M11V 和半合子男性中的无义突变 R190X。
Two novel alpha-galactosidase A mutations causing Fabry disease: A missense mutation M11V in a heterozygote woman and a nonsense mutation R190X in a hemizygote man.
机构信息
Hacettepe University, Faculty of Medicine, Department of Medical Biochemistry, 06100, Ankara, Turkey.
出版信息
Clin Biochem. 2011 Jul;44(10-11):809-12. doi: 10.1016/j.clinbiochem.2011.04.022. Epub 2011 May 4.
OBJECTIVES
To evaluate the nature of the molecular lesions in the alpha-galactosidase A gene of two patients having Fabry disease.
METHODS
Enzyme analyses were done using 4-methylumbellyferyl alpha-galactoside as substrate. Single stranded conformational polymorphism analysis and DNA sequencing were performed following PCR amplification of seven exons of alpha-galactosidase A gene.
RESULTS
Two new mutations, M11V and R190X, were identified. The female patient with M11V mutation had rheumatologic symptoms, microalbuminuria. The male patient with R190X mutation had a classical phenotype. M11V mutation is in the signal sequence of the peptide and may affect the targeting of the ribosomes to ER. R190X mutation causes premature termination, and probably leads to degradation of the protein.
CONCLUSION
This is the first study in our country investigating the molecular aspects of Fabry disease. It provides the molecular basis for understanding the underlying mechanism of Fabry disease, allows prenatal diagnosis and provides genotype/phenotype correlations.
目的
评估两名法布里病患者α-半乳糖苷酶 A 基因分子病变的性质。
方法
使用 4-甲基伞形酮-α-半乳糖苷作为底物进行酶分析。在对α-半乳糖苷酶 A 基因的七个外显子进行 PCR 扩增后，进行单链构象多态性分析和 DNA 测序。
结果
发现了两个新的突变，M11V 和 R190X。携带 M11V 突变的女性患者有风湿症状和微量白蛋白尿。携带 R190X 突变的男性患者具有典型的表型。M11V 突变位于肽的信号序列中，可能影响核糖体向内质网的靶向。R190X 突变导致过早终止，可能导致蛋白质降解。
结论
这是我国首次研究法布里病的分子方面。它为了解法布里病的潜在机制提供了分子基础，允许进行产前诊断，并提供基因型/表型相关性。
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