The molecular basis of UDP-galactose-4-epimerase (GALE) deficiency galactosemia in Korean patients
The molecular basis of UDP-galactose-4-epimerase (GALE) deficiency galactosemia in Korean patients
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DOI：
10.1097/01.gim.0000194023.27802.2d
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发表时间：
2005-11-01
影响因子：
8.8
通讯作者：
Song, JH
中科院分区：
文献类型：
--
作者：
Park, HD;Park, KU;Song, JH
目的：UDP-半乳糖-4-差向异构酶（GALE）缺乏性半乳糖血症是一种常染色体隐性遗传疾病，其患病率在不同种族群体之间存在差异。我们的目的是探讨韩国患者的分子特征与减弱GALE活动和升高的半乳糖-1-磷酸levels in blood.Methods：为了表征潜在的GALE缺陷的分子缺陷，GALE基因的7例患者表现出严重的活动下降进行测序。结果：共检测到9个突变：8个错义突变（p.A25V、p.R40C、p.D69E、p.E165K、p.R169W、p.R239W、p.G302D和p.R335H）和1个无义突变（p.W336X）。除了p.R335H，所有这些突变都是新的。6例患者为复合杂合子（p.D69E/p.G302D、p.R40C/p.R169W、p.D69E/p.E165K、p.R239W/p.R335H、p.A25V/p.RI69W和p.G302D/p.R335H），其余患者仅存在1个突变（p.W336X/未检出）。30例GALE活性中度降低的患者也通过PCR-RFLP检测上述突变的存在，在这30例患者中的17例中检测到突变。结论：我们在韩国半乳糖血症患者中检测到9种GALE基因突变，证实了该疾病的等位基因异质性。
Purpose: UDP-galactose-4-epimerase (GALE) deficiency galactosemia is an autosomal recessive disorder and the prevalence of the disease varies among ethnic groups. We aimed to investigate molecular characteristics of the Korean patients with attenuated GALE activity and elevated galactose-1-phosphate levels in blood.Methods: In order to characterize the molecular defects underlying GALE deficiency, the GALE gene of 7 patients showing severe activity decreases was sequenced. PCR-RFLP was performed to confirm the presence of the mutations identified by sequencing.Results: Nine mutations were identified: 8 missense mutations (p.A25V, p.R40C, p.D69E, p.E165K, p.R169W, p.R239W, p.G302D, and p.R335H) and one nonsense mutation (p.W336X). Except for p.R335H, all of these mutations are novel. Six patients were compound heterozygotes (p.D69E/p.G302D, p.R40C/p.R169W, p.D69E/p.E165K, p.R239W/p.R335H, p.A25V/p.RI69W, and p.G302D/p.R335H) and the remaining patient had only one mutation (p.W336X/not detected). Thirty patients with moderately reduced GALE activity were also tested by PCR-RFLP for the presence of the above mutation, and mutations were detected in 17 of these 30 patients. The frequency of p.G302D (9/30), p.R239W (6/30) and p.R169W (5/30) in our Korean patients with GALE deficiency galactosemia was relatively high.Conclusions: We detected 9 mutations of the GALE gene in Korean galactosemia patients, and confirmed allelic heterogeneity in this disease.