Bae Sun Hwan, Kim Jong Won, Seo Jeong Kee
Division of Pediatric Gastroenterology, Hepatology and Nutrition, School of Medicine, Seoul National University, Korea.
Korean J Hepatol. 2009 Sep;15(3):309-19. doi: 10.3350/kjhep.2009.15.3.309.
BACKGROUND/AIMS: Wilson's disease (WD) is an inherited disorder of copper metabolism caused by alteration of the P-type adenosine triphosphatase (ATP) 7B gene. In this study, we analyzed the frequency of well-known mutations and constructed the first haplotypes for Koreans. In addition, we evaluated whether a founder effect existed in Korean patients with WD.
We obtained DNA samples from 21 patients with WD and their parents (total cohort n=63). ATP7B gene mutations were identified by direct sequencing methods, and microsatellite typing was performed at D13S315, D13S1325, and D13S316 with fluorescent dye-labeled primers. Any founder effect was identified by using 42 normal alleles from parents with a normal phenotype as a control group. The chi square test and Fisher's exact test were used for statistical analysis.
Three common mutations were found in 23 chromosomes obtained from 21 patients: the R778L mutation at exon 8 (15/23, 65.2%), the A874V mutation at exon 11 (6/23, 26.1%), and the N1270S mutation at exon 18 (2/23, 8.7%). D13S315 and D13S316 showed linkage disequilibrium at alleles 5 and 4, respectively, in patients with the R778L mutation (P=0.0157 and 0.0001, respectively). The haplotype made up of these two alleles occurred significantly more frequently in patients with the R778L mutation (5-R778L-4, D13S315-mutation-D13S316) than in the controls (P=0.0018).
The arche haplotype of the ATP7B gene in Korean patients with WD may be 5-R778L-4 (D13S315.mutation.D13S316), and it might illustrate a founder effect.
背景/目的：威尔逊病（WD）是一种由P型腺苷三磷酸酶（ATP）7B基因改变引起的铜代谢遗传性疾病。在本研究中，我们分析了常见突变的频率，并构建了韩国人的首个单倍型。此外，我们评估了韩国WD患者中是否存在奠基者效应。
我们从21例WD患者及其父母（总队列n = 63）中获取DNA样本。通过直接测序方法鉴定ATP7B基因突变，并使用荧光染料标记引物在D13S315、D13S1325和D13S316处进行微卫星分型。以42个来自表型正常父母的正常等位基因作为对照组来鉴定任何奠基者效应。采用卡方检验和Fisher精确检验进行统计分析。
从21例患者获得的23条染色体中发现了三种常见突变：外显子8的R778L突变（15/23，65.2%）、外显子11的A874V突变（6/23，26.1%）和外显子18的N1270S突变（2/23，8.7%）。在R778L突变患者中，D13S315和D13S316分别在等位基因5和4处显示连锁不平衡（P分别为0.0157和0.0001）。由这两个等位基因组成的单倍型在R778L突变患者（5-R778L-4，D13S315-突变-D13S316）中出现的频率显著高于对照组（P = 0.0018）。
韩国WD患者中ATP7B基因的典型单倍型可能是5-R778L-4（D13S315.突变.D13S316），这可能说明了奠基者效应。
