韩国半乳糖-1-磷酸尿苷酰转移酶缺乏症患者 GALT 基因的分子和生化特征。
Molecular and biochemical characterization of the GALT gene in Korean patients with galactose-1-phosphate uridyltransferase deficiency.
机构信息
Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, South Korea.
出版信息
Clin Chim Acta. 2010 Oct 9;411(19-20):1506-10. doi: 10.1016/j.cca.2010.06.008. Epub 2010 Jun 11.
BACKGROUND
Three different types of galactosemia have been described, and the most common form occurs due to a deficiency in the galactose-1-phosphate uridyltransferase (GALT) enzyme activity.
METHODS
To investigate the molecular defects of the GALT gene, PCR-direct sequencing was performed with genomic DNA from 18 Korean patients with reduced GALT activity.
RESULTS
Of the 18 patients tested, 13 (72.2%) had previously reported variants: Duarte variant (12 patients), p.R201H (1 patient), and g.A1962G. In addition, we identified six novel sequence variations by PCR-direct sequencing: five sequence variations in coding regions (p.H31R, p.L116I, p.Q169H, p.H186P and p.R333R), and one in an intron (g.2621A>G). Of 100 normal individuals tested, 4 were heterozygous for the Duarte variant, which indicates a Duarte allele frequency of 2%. Biochemical characteristics of the novel genetic alterations were determined: enzyme activity for exonic alterations and splicing for intron.
CONCLUSION
The genetic constitution of the GALT gene is responsible for galactosemia in the Korean population.
背景
已描述了三种不同类型的半乳糖血症，最常见的形式是由于半乳糖-1-磷酸尿苷酰转移酶（GALT）酶活性缺乏所致。
方法
为了研究 GALT 基因的分子缺陷，我们对 18 名韩国 GALT 活性降低患者的基因组 DNA 进行了 PCR 直接测序。
结果
在 18 名受检患者中，有 13 名（72.2%）患者存在先前报道的变异：Duarte 变异（12 名患者）、p.R201H（1 名患者）和 g.A1962G。此外，我们通过 PCR 直接测序鉴定了六个新的序列变异：五个编码区的序列变异（p.H31R、p.L116I、p.Q169H、p.H186P 和 p.R333R）和一个内含子的序列变异（g.2621A>G）。在 100 名正常个体中，有 4 名为 Duarte 变异的杂合子，表明 Duarte 等位基因的频率为 2%。我们确定了新遗传改变的生化特征：外显子改变的酶活性和内含子改变的剪接。
结论
GALT 基因的遗传构成是导致韩国人群半乳糖血症的原因。
Zotero 插件